Journal articles on the topic 'BMP'
To see the other types of publications on this topic, follow the link: BMP.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'BMP.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Pascual, V., Y. J. Liu, A. Magalski, O. de Bouteiller, J. Banchereau, and J. D. Capra. "Analysis of somatic mutation in five B cell subsets of human tonsil." Journal of Experimental Medicine 180, no. 1 (July 1, 1994): 329–39. http://dx.doi.org/10.1084/jem.180.1.329.
Abstract:
Using a series of phenotypic markers that include immunoglobulin (Ig)D, IgM, IgG, CD23, CD44, Bcl-2, CD38, CD10, CD77, and Ki67, human tonsillar B cells were separated into five fractions representing different stages of B cell differentiation that included sIgD+ (Bm1 and Bm2), germinal center (Bm3 and Bm4), and memory (Bm5) B cells. To establish whether the initiation of somatic mutation correlated with this phenotypic characterization, we performed polymerase chain reaction and subsequent sequence analysis of the Ig heavy chain variable region genes from each of the B cell subsets. We studied the genes from the smallest VH families (VH4, VH5, and VH6) in order to facilitate the mutational analysis. In agreement with previous reports, we found that the somatic mutation machinery is activated only after B cells reach the germinal center and become centroblasts (Bm3). Whereas 47 independently rearranged IgM transcripts from the Bm1 and Bm2 subsets were nearly germline encoded, 57 Bm3-, and Bm4-, and Bm5-derived IgM transcripts had accumulated an average of 5.7 point mutations within the VH gene segment. gamma transcripts corresponding to the same VH gene families were isolated from subsets Bm3, Bm4, and Bm5, and had accumulated an average of 9.5 somatic mutations. We conclude that the molecular events underlying the process of somatic mutation takes place during the transition from IgD+, CD23+ B cells (Bm2) to the IgD-, CD23-, germinal center centroblast (Bm3). Furthermore, the analysis of Ig variable region transcripts from the different subpopulations confirms that the pathway of B cell differentiation from virgin B cell throughout the germinal center up to the memory compartment can be traced with phenotypic markers. The availability of these subpopulations should permit the identification of the functional molecules relevant to each stage of B cell differentiation.
2
Pekkarinen, Tarmo, T. Sam Lindholm, Aulis Marttinen, Oili Hietala, and Pekka Jalovaara. "INFLUENCE OF ETHYLENE OXIDE STERILIZATION ON NEW BONE FORMATION INDUCED BY BOVINE BONE MORPHOGENETIC PROTEIN." Journal of Musculoskeletal Research 04, no. 04 (December 2000): 287–95. http://dx.doi.org/10.1142/s021895770000032x.
Abstract:
Bone morphogenetic proteins (BMPs) have the capacity to induce and accelerate bone regeneration. Before experimental and clinical settings, BMP must be sterilized. Ethylene oxide (EO) gas sterilizations at different temperatures are commonly used but the effects of that on the osteoinductive capacity of BMP have been the subject of controversy. Here, we investigated the effects of three different EO sterilization methods on the osteoinductivity of partially purified native bovine BMP (bBMP). Gelatin capsules containing 3 mg of bBMP were sterilized as follows: (i) manually inside a dessicator with 12% EO spray (20°C, exposure time 2 h); (ii) with an EO gas sterilizer (Steri-Vac 4XL, temperature 29°C, exposure time 4 h 10 min, ethylene oxide concentration 860 mg/l); (iii) with an EO gas sterilizer (Steri-Vac 5XL, temperature 42°C, exposure time 3 h, ethylene oxide concentration 700 mg/l). The sterilization processes were monitored with samples of Bacillus subtilis (3M, Attest 1264). Osteoinductivity of bBMP was verified by bioassay. After 21 days of implantation of bBMP into the muscle pouches of mice, the animals were killed and new bone formation was measured radiographically and histologically. The EO sterilization techniques used did not significantly decrease the osteoinductive activity of BMP. It is concluded that commercial EO gas equipment sterilization is effective for sterilized BMP and does not decrease the osteoinductive capacity of bovine BMP.
3
Ping, Tsu-Ni, Shu-Ling Hsieh, Jyh-Jye Wang, Jin-Bor Chen, and Chih-Chung Wu. "Panax notoginseng Suppresses Bone Morphogenetic Protein-2 Expression in EA.hy926 Endothelial Cells by Inhibiting the Noncanonical NF-κB and Wnt/β-Catenin Signaling Pathways." Plants 11, no. 23 (November 28, 2022): 3265. http://dx.doi.org/10.3390/plants11233265.
Abstract:
Panax notoginseng (PN) exerts cardiovascular-disease-protective effects, but the effect of PN on reducing vascular calcification (VC) is unknown. Under the VC process, however, endothelial bone morphogenetic protein-2 (BMP-2) signals connect endothelial and smooth muscle cells. To investigate the effects of PN water extract (PNWE) on BMP-2 expression, human EA.hy926 endothelial cells were pretreated with PNWE for 48 h, and BMP-2 expression was then induced using warfarin/β-glycerophosphate (W/BGP) for another 24 h. The expression of BMP-2, the degrees of oxidative stress and inflammation, and the activation of noncanonical NF-κB and Wnt/β-catenin signaling were analyzed. The results showed that the BMP-2 levels in EA.hy926 cells were reduced in the groups treated with 10, 50, or 100 μg/mL PNWE combined with W/BGP. PNWE combined with W/BGP significantly reduced thiobarbituric-acid-reactive substrate and reactive oxygen species levels as well as prostaglandin E2, IL-1β, IL-6, and TNF-α. PNWE (10, 50, and 100 μg/mL) reduced the p52 levels and p52/p100 protein ratio. Wnt and β-catenin protein expression was decreased in the groups treated with PNWE combined with W/BGP. These results showed that PNWE reduced BMP-2 expression in EA.hy926 cells by inhibiting the noncanonical NF-κB and Wnt/β-catenin signaling pathways.
4
Lim, Hyun-Chang, Daniel S. Thoma, So-Ra Yoon, Jae-Kook Cha, Jung-Seok Lee, and Ui-Won Jung. "Bone Regeneration Using N-Methyl-2-pyrrolidone as an Enhancer for Recombinant Human Bone Morphogenetic Protein-2 in a Rabbit Sinus Augmentation Model." BioMed Research International 2017 (2017): 1–8. http://dx.doi.org/10.1155/2017/4153073.
Abstract:
The aim of this study was to determine whether N-methyl-2-pyrrolidone (NMP) can decrease the dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) in sinus augmentation of rabbits. In each of 15 rabbits, 2 sinuses were randomly grafted using 1 of 3 treatment modalities: (i) biphasic calcium phosphate (BCP; control), (ii) rhBMP-2-coated BCP (BMP), or (iii) rhBMP-2-coated BCP soaked in NMP solution (BMP/NMP). The rabbits were sacrificed 2 weeks postoperatively. Histologic and histomorphometric analyses were performed. Bone formation in all groups was predominantly located close to the access window and the lateral walls. Newly formed bone within the total augmented area (NBTA) was greatest in BMP/NMP (1.94±0.69 mm2), followed by BMP (1.50±0.72 mm2) and BCP (1.28±0.52 mm2) (P>0.05). In the center of the augmentation (NBROI_C) and the area close to the sinus membrane (NBROI_M), BMP/NMP produced the largest area of NB (NBROI_C: 0.10±0.11 mm2; NBROI_M: 0.17±0.08 mm2); the corresponding NB values for BCP were 0.05±0.05 mm2 and 0.08±0.09 mm2, respectively (P>0.05 for all comparisons). The effect of NMP on bone regeneration was inconsistent between the specimens. Adding NMP as an adjunct to rhBMP-2-coated BCP produced inconsistent effects on bone regeneration, resulting in no significant benefit compared to controls.
5
Glaeser, Juliane D., Khosrowdad Salehi, Linda EA Kanim, Derek G. Ju, Jae Hyuk Yang, Phillip H. Behrens, Samuel A. Eberlein, et al. "Electrospun, synthetic bone void filler promotes human MSC function and BMP-2 mediated spinal fusion." Journal of Biomaterials Applications 35, no. 4-5 (July 5, 2020): 532–43. http://dx.doi.org/10.1177/0885328220937999.
Abstract:
Introduction Synthetic bone grafts are often used to achieve a well-consolidated fusion mass in spinal fusion procedures. These bone grafts function as scaffolds, and ideally support cell function and facilitate protein binding. Objective The aim was to characterize an electrospun, synthetic bone void filler (Reb) for its bone morphogenetic protein (BMP)-2 release properties and support of human mesenchymal stem cell (hMSC) function in vitro, and its efficacy in promoting BMP-2-/bone marrow aspirate-(BMA)-mediated posterolateral spinal fusion (PLF) in vivo. Methods BMP-2 release kinetics from Reb versus standard absorbable collagen sponge (ACS) was determined. hMSC adhesion and proliferation on Reb was tested using cell counting, fluorescence microscopy and MTS. Cell osteogenic differentiation was quantified via cellular alkaline phosphatase (ALP) activity. For in vivo analysis, 18 Lewis rats were treated during PLF surgery with the following groups: (I) Reb + BMA, (II) Reb + BMA + BMP-2 and (III) BMA. A safe, minimally effective dose of BMP-2 was used. Fusion consolidation was followed for 3 months using radiography and micro-CT. After sacrifice, fusion rate and biomechanical stiffness was determined using manual palpation, biomechanical tests and histology. Results In vitro, BMP-2 release kinetics were similar between Reb versus ACS. MSC proliferation and differentiation were increased in the presence of Reb. At 3 months post-surgery, fusion rates were 29% (group I), 100% (group II), and 0% (group III). Biomechanical stiffness was higher in group II versus I. Micro-CT showed an increased bone volume and connectivity density in group II. Trabecular thickness was increased in group I versus II. H&E staining showed newly formed bone in group II only. Conclusions Reb possesses a high protein binding affinity and promotes hMSC function. Combination with BMA and minimal dose BMP-2 allowed for 100% bone fusion in vivo. This data suggests that a minimally effective dose of BMP-2 can be used when combined with Reb.
6
Lakdawala, Mohammed Farhan, Bhoomi Madhu, Lionel Faure, Mehul Vora, Richard W. Padgett, and Tina L. Gumienny. "Genetic interactions between the DBL-1/BMP-like pathway and dpy body size–associated genes in Caenorhabditis elegans." Molecular Biology of the Cell 30, no. 26 (December 15, 2019): 3151–60. http://dx.doi.org/10.1091/mbc.e19-09-0500.
Abstract:
How BMP signaling and other body size regulators interact is not clear. We found interactions between Caenorhabditis elegans DBL-1/BMP and ECM, proteins that may modify or secrete DBL-1, and the SET domain protein BLMP-1. DBL-1 signaling may control downstream targets, some through BLMP-1, that affect size either directly or by feeding back on DBL-1 signaling.
7
Cheng, Gang, Hong Chen, Kai Wang, Jinxing Gao, Xiao Li, Hui Dong, and Shuyan Liu. "Biphasic Calcium Phosphate/Chitosan/Polyacrylonitrile/Polylactic Acid-Glycolic Acid (PLGA) Nanocomposite Stent for Repair and Osteogenesis of Oral Alveolar Bone Defect." Science of Advanced Materials 13, no. 7 (July 1, 2021): 1324–34. http://dx.doi.org/10.1166/sam.2021.4039.
Abstract:
ABSTRACTThe ability of sol-gel micro-nano biphasic calcium stent to repair oral alveolar bone defects was investigated in this study, and its osteogenesis performance was also analyzed. Biphasic calcium phosphate (BCP) was synthesized by wet method, which was combined with chitosan (CS), polyacrylonitrile (PAN), and polylactic acid-glycolic acid (PLGA). Then, the BCP/CS/PAN/PLGA nanocomposite stent was prepared by vacuum freeze-drying technology. The micro-nano composite stent was combined with the bone morphogenetic protein-2 (BMP-2) gene, so as to obtain the sol-gel micro-nano biphasic calcium BMP-2/BCP/CS/PAN/PLGA composite stent. Besides, the composite stent should be measured in terms of compressive strength, porosity, structure, and morphological features. The healthy female rhesus monkeys were taken as the research animals, and the iliac bone marrow was extracted by puncture. The mesenchymal stem cells (MSCs) were obtained by density gradient centrifugation, and their osteogenic differentiation ability was observed. The MSCs were cultured in vitro with BMP-2/BCP/CS/PAN/PLGA composite stent, methylthiazolyldiphenyl-tetrazolium bromide (MTT) was applied to detect cell adhesion and proliferation, and the alkaline phosphatase (ALP) activity was employed to analyze its osteogenic properties on stent materials. In addition, the expression of BMP-2 was detected by Western blot. The alveolar bone defect models were established and divided into group A (MSCs + BMP-2/BCP/CS/PAN/PLGA), group B (BMP-2/BCP/CS/PAN/PLGA), group C (BCP/CS/PAN/PLG), and group D (control group, reposition of gingival flap and suture) according to different implant materials. The changes of bone defect area in different groups were detected by gross examinations and X-ray, so that the new bone density was analyzed. The results showed that the BCP/CS/PAN/PLGA composite stent exhibited a porous structure combining multiple pores/small pores, with an average pore diameter (PD) of 400–500 µm, maximum compressive strength of 6.02 Mpa, and porosity of 86.82%. MSCs differentiated into osteoblasts under osteogenic induction conditioned medium, and the optical density (OD) of CS + MSCs/BMP-2/BCP/CS/PAN/PLGA cells was greater in contrast to that of MSCs/BMP-2/BCP/CS/PAN/PLGA cells on the 1st and 7th day of culture, showing a statistical difference (P < 0.05). The gross examination and X-ray of bone defect area in group A showed that its bone structure and density were very close to those of normal bone (all materials were absorbed, and newly formed bone cells were active); the CT value of alveolar bone in groups A, B, C, and D was 1,092.45± 15.87 g/cm3, 932.26± 16.75 g/cm3, 859.51 ±17.86 g/cm3, and 787.96± 16.54 g/cm3, respectively. There was no marked difference in CT values between group A and normal alveolar bone (P > 0.05), while the CT value of alveolar bone in group A was higher obviously than the value of groups C and D (P < 0.05). It indicated that the composite stent based on sol–gel micro-nano biphasic calcium BMP-2/BCP/CS/PAN/PLGA could promote the repair of oral alveolar bone defect and its osteogenesis, thereby providing a reference for the oral clinical treatment of periodontal bone defects.
8
Ammar, Hany R., Subbarayan Sivasankaran, and Abdulaziz S. Alaboodi. "Investigation of the Microstructure and Compressibility of Biodegradable Fe-Mn-Cu/W/Co Nanostructured Alloy Powders Synthesized by Mechanical Alloying." Materials 14, no. 11 (June 4, 2021): 3088. http://dx.doi.org/10.3390/ma14113088.
Abstract:
In this research work, the nanostructured Fe-Mn (BM0), Fe-Mn-Cu (BM1), Fe-Mn-W (BM2), and Fe-Mn-Co (BM3) biodegradable alloys were successfully synthesized using mechanical alloying. The microstructure of the synthesized alloys was examined using XRD, SEM equipped with EDS, and HRTEM techniques. The results obtained based on these techniques confirmed the development of nanostructured BM0, BM1, BM2, and BM3 alloys and homogenous solid solutions with an even elemental dispersion. The compressibility of the synthesized alloys was investigated experimentally and empirically in the as-milled conditions and after applying a stress relief treatment (150 °C for 1 h). The load applied for compaction experiments ranged from 25–1100 MPa with a rate of 1 mm/min. According to the experimentation performed in the current study, the relative density of the as-milled BM0, BM1, BM2, and BM3 alloys was 72.90% and 71.64%, 72.32%, and 72.03%, respectively. After applying the stress relief treatment, the density was observed to increase to 75.23%, 77.10%, 72.65%, and 72.86% for BM0-S, BM1-S, BM2-S and BM3-S samples, respectively. A number of compaction models were tested to identify the optimum models for predicting the compressibility behavior of nanostructured Fe-Mn, Fe-Mn-Cu, Fe-Mn-W, and Fe-Mn-Co alloys in the as-milled and stress-relieved conditions.
9
Song, Sang-Heon, Young-Pil Yun, Hak-Jun Kim, Kyeongsoon Park, Sung Eun Kim, and Hae-Ryong Song. "Bone Formation in a Rat Tibial Defect Model Using Carboxymethyl Cellulose/BioC/Bone Morphogenic Protein-2 Hybrid Materials." BioMed Research International 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/230152.
Abstract:
The objective of this study was to assess whether carboxymethyl cellulose- (CMC-) based hydrogel containing BioC (biphasic calcium phosphate (BCP); tricalcium phosphate (TCP) : hydroxyapatite (Hap) = 70 : 30) and bone morphogenic protein-2 (BMP-2) led to greater bone formation than CMC-based hydrogel containing BioC without BMP-2. In order to demonstrate bone formation at 4 and 8 weeks, plain radiographs, microcomputed tomography (micro-CT) evaluation, and histological studies were performed after implantation of all hybrid materials on an 8 mm defect of the right tibia in rats. The plain radiographs and micro-CT analyses revealed that CMC/BioC/BMP-2 (0.5 mg) led to much greater mineralization at 4 and 8 weeks than did CMC/BioC or CMC/Bio/BMP-2 (0.1 mg). Likewise, bone formation and bone remodeling studies revealed that CMC/BioC/BMP-2 (0.5 mg) led to a significantly greater amount of bone formation and bone remodeling at 4 and 8 weeks than did CMC/BioC or CMC/BioC/BMP-2 (0.1 mg). Histological studies revealed that mineralized bone tissue was present around the whole circumference of the defect site with CMC/BioC/BMP-2 (0.5 mg) but not with CMC/BioC or CMC/BioC/BMP-2 (0.1 mg) at 4 and 8 weeks. These results suggest that CMC/BioC/BMP-2 hybrid materials induced greater bone formation than CMC/BioC hybrid materials. Thus, CMC/BioC/BMP-2 hybrid materials may be used as an injectable substrate to regenerate bone defects.
10
Mehryar, Esmaeil, Weimin Ding, Abbas Hemmat, Muhammad Hassan, Zahir Talha, Jalal Kafashan, and Hongying Huang. "Modeling and Multiresponse Optimization for Anaerobic Codigestion of Oil Refinery Wastewater and Chicken Manure by Using Artificial Neural Network and the Taguchi Method." BioMed Research International 2017 (2017): 1–15. http://dx.doi.org/10.1155/2017/2036737.
Abstract:
To study the optimum process conditions for pretreatments and anaerobic codigestion of oil refinery wastewater (ORWW) with chicken manure, L9 (34) Taguchi’s orthogonal array was applied. The biogas production (BGP), biomethane content (BMP), and chemical oxygen demand solubilization (CODS) in stabilization rate were evaluated as the process outputs. The optimum conditions were obtained by using Design Expert software (Version 7.0.0). The results indicated that the optimum conditions could be achieved with 44% ORWW, 36°C temperature, 30 min sonication, and 6% TS in the digester. The optimum BGP, BMP, and CODS removal rates by using the optimum conditions were 294.76 mL/gVS, 151.95 mL/gVS, and 70.22%, respectively, as concluded by the experimental results. In addition, the artificial neural network (ANN) technique was implemented to develop an ANN model for predicting BGP yield and BMP content. The Levenberg-Marquardt algorithm was utilized to train ANN, and the architecture of 9-19-2 for the ANN model was obtained.
11
ROSEN, V. "BMP and BMP Inhibitors in Bone." Annals of the New York Academy of Sciences 1068, no. 1 (April 1, 2006): 19–25. http://dx.doi.org/10.1196/annals.1346.005.
12
Aguiar, Antônio S. N., Pablo G. M. Dias, Jaqueline E. Queiroz, Pollyana P. Firmino, Jean M. F. Custódio, Lucas D. Dias, Gilberto L. B. Aquino, Ademir J. Camargo, and Hamilton B. Napolitano. "Insights on Potential Photoprotective Activity of Two Butylchalcone Derivatives: Synthesis, Spectroscopic Characterization and Molecular Modeling." Photonics 10, no. 3 (February 21, 2023): 228. http://dx.doi.org/10.3390/photonics10030228.
Abstract:
The development of photoprotective agents presents a growing interest due to skin disorders, e.g., cancer. In order to obtain natural-based compounds with potential photoprotective activity, we promote the synthesis and extensive characterization of a butylchalcone derivative (E)-3-(4-butylphenyl)-1-(4-methylphenyl)-prop-2-en-1-one (BMP). Moreover, we carried out a comparative analysis of two chalcones bearing a methyl (BMP) and bromo (BBP) substituent groups (at para position), on respective electronic structures and supramolecular arrangement, using density functional theory (DFT). Through theoretical calculations carried out by DFT, it was possible to verify its antioxidant property by the mechanisms of free radical scavenging, H-atom transfer (HAT), and one-electron transfer (ET), and their stabilities. Finally, from the analysis of chalcone’s electronic transitions in the excited state calculated by the time-dependent (TD)-DFT method as well as UV-vis absorption spectra of the BMP and BBP (200–390 nm), it is possible to highlight their potential use as organic photoprotective agents.
13
Martinez-Valdez, H., C. Guret, O. de Bouteiller, I. Fugier, J. Banchereau, and Y. J. Liu. "Human germinal center B cells express the apoptosis-inducing genes Fas, c-myc, P53, and Bax but not the survival gene bcl-2." Journal of Experimental Medicine 183, no. 3 (March 1, 1996): 971–77. http://dx.doi.org/10.1084/jem.183.3.971.
Abstract:
During T cell-dependent antibody responses, B cells within germinal centers (GC) alter the affinity of their antigen receptor by introducing somatic mutations into variable region of immunoglobulin (IgV) genes. During this process, GC B cells are destined to die unless positively selected by antigens and CD40-ligand. To understand survival/death control of germinal center B cell, the expression of four apoptosis-inducing genes, Fas, c-myc, Bax, and P53, together with the survival gene bcl-2, has been analyzed herein among purified tonsillar naive, GC, and memory B cells. IgD+CD38- naive B cells were separated into CD23- (mature B cell [Bm]1) subset and CD23+ (Bm2), IgD-CD38+ GC B cells were separated into subsets of CD77+ centroblasts (Bm3) and CD77- centrocytes (Bm4), whereas IgD-CD38- cells represented the Bm5 memory B cell subset. Sequence analysis of IgV region genes indicated that somatic hypermutation was triggered in the Bm3 centroblast subset. Here we show that bcl-2 is only detectable with naive (Bm1 and 2) and memory B cell (Bm5) subsets, whereas all four apoptosis-inducing genes were most significantly expressed within GC B cells. Fas was equally expressed in Bm3 centroblasts and Bm4 centrocytes, whereas Bax was most significantly expressed in Bm4 centrocytes. c-myc, a positive regulator of cell cycle, was most significantly expressed in proliferating Bm3 centroblasts, whereas P53, a negative regulator of cell cycle, was most signficantly expressed in nonproliferating Bm4 centrocytes. The present results indicate that the survival/death of GC B cells are regulated by the up- and downregulation of multiple genes, among which the expression of c-myc and P53 in the absence of bcl-2 may prime the proliferating Bm3 centroblasts and nonproliferating Bm4 centrocytes to apoptosis.
14
Kim, So-Yeun, Eun-Bin Bae, Jae-Woong Huh, Jong-Ju Ahn, Hyun-Young Bae, Won-Tak Cho, and Jung-Bo Huh. "Bone Regeneration Using a Three-Dimensional Hexahedron Channeled BCP Block Combined with Bone Morphogenic Protein-2 in Rat Calvarial Defects." Materials 12, no. 15 (July 31, 2019): 2435. http://dx.doi.org/10.3390/ma12152435.
Abstract:
It is important to obtain sufficient bone mass before implant placement on alveolar bone, and synthetic bone such as biphasic calcium phosphate (BCP) has been studied to secure this. This study used a BCP block bone with a specific structure of the three-dimensional (3D) hexahedron channel and coating with recombinant human bone morphogenetic protein-2 (rhBMP-2) impregnated carboxymethyl cellulose (CMC) was used to examine the enhancement of bone regeneration of this biomaterial in rat calvarial defect. After the preparation of critical-size calvarial defects in fifteen rats, defects were divided into three groups and were implanted with the assigned specimen (n = 5): Boneplant (untreated 3D hexahedron channeled BCP block), Boneplant/CMC (3D hexahedron channeled BCP block coated with CMC), and Boneplant/CMC/BMP (3D hexahedron channeled BCP block coated with CMC containing rhBMP-2). After 4 weeks, the volumetric, histologic, and histometric analyses were conducted to measure the newly formed bone. Histologically, defects in the Boneplant/CMC/BMP group were almost completely filled with new bone compared to the Boneplant and Boneplant/CMC groups. The new bone volume (P < 0.05) and area (P < 0.001) in the Boneplant/CMC/BMP group (20.12% ± 2.17, 33.79% ± 3.66) were much greater than those in the Boneplant (10.77% ± 4.8, 16.48% ± 9.11) and Boneplant/CMC (10.72% ± 3.29, 16.57% ± 8.94) groups, respectively. In conclusion, the 3D hexahedron channeled BCP block adapted rhBMP-2 with carrier CMC showed high possibility as an effective bone graft material.
15
&NA;. "BMP-2." Reactions Weekly &NA;, no. 1345 (April 2011): 9–10. http://dx.doi.org/10.2165/00128415-201113450-00027.
16
Malmquist, Jay P. "Recombinant–BMP." Journal of Oral and Maxillofacial Surgery 67, no. 9 (September 2009): 8. http://dx.doi.org/10.1016/j.joms.2009.05.313.
17
Danesh, Shahab M., Alethia Villasenor, Diana Chong, Carrie Soukup, and Ondine Cleaver. "BMP and BMP receptor expression during murine organogenesis." Gene Expression Patterns 9, no. 5 (June 2009): 255–65. http://dx.doi.org/10.1016/j.gep.2009.04.002.
18
Kim, Yongsun, Byung-Jae Kang, Wan Kim, Hui-suk Yun, and Oh-kyeong Kweon. "Evaluation of Mesenchymal Stem Cell Sheets Overexpressing BMP-7 in Canine Critical-Sized Bone Defects." International Journal of Molecular Sciences 19, no. 7 (July 17, 2018): 2073. http://dx.doi.org/10.3390/ijms19072073.
Abstract:
The aim of this study was to investigate the in vitro osteogenic capacity of bone morphogenetic protein 7 (BMP-7) overexpressing adipose-derived (Ad-) mesenchymal stem cells (MSCs) sheets (BMP-7-CS). In addition, BMP-7-CS were transplanted into critical-sized bone defects and osteogenesis was assessed. BMP-7 gene expressing lentivirus particles were transduced into Ad-MSCs. BMP-7, at the mRNA and protein level, was up-regulated in BMP-7-MSCs compared to expression in Ad-MSCs. Osteogenic and vascular-related gene expressions were up-regulated in BMP-7-CS compared to Ad-MSCs and Ad-MSC sheets. In a segmental bone-defect model, newly formed bone and neovascularization were enhanced with BMP-7-CS, or with a combination of BMP-7-CS and demineralized bone matrix (DBM), compared to those in control groups. These results demonstrate that lentiviral-mediated gene transfer of BMP-7 into Ad-MSCs allows for stable BMP-7 production. BMP-7-CS displayed higher osteogenic capacity than Ad-MSCs and Ad-MSC sheets. In addition, BMP-7-CS combined with demineralized bone matrix (DBM) stimulated new bone and blood vessel formation in a canine critical-sized bone defect. The BMP-7-CS not only provides BMP-7 producing MSCs but also produce osteogenic and vascular trophic factors. Thus, BMP-7-CS and DBM have therapeutic potential for the treatment of critical-sized bone defects and could be used to further enhance clinical outcomes during bone-defect treatment.
19
Rohanizadeh, Ramin, and Kimberly Chung. "Hydroxyapatite as a Carrier for Bone Morphogenetic Protein." Journal of Oral Implantology 37, no. 6 (December 1, 2011): 659–72. http://dx.doi.org/10.1563/aaid-joi-d-10-00005.
Abstract:
Bone morphogenetic proteins (BMPs) can induce the formation of new bone in numerous orthopedic and dental applications in which loss of bone is the main issue. The combination of BMP with a biomaterial that can carry and deliver proteins has been demonstrated to maximize the therapeutic effects of BMPs. However, no ideal candidate with optimal characteristics as a carrier has emerged for clinical use of BMPs. Hydroxyapatite (HA) is a potential BMP carrier with its osteoconductive properties and desirable characteristics as a bone graft biomaterial. In this study, 3 different methods to load BMP into HA materials were characterized and compared based on the BMP uptake and release profile. BMP was loaded into HA in 3 ways: (1) incorporation of BMP during HA precipitation, (2) HA immersion in BMP solution, and (3) BMP incorporation during dicalcium phosphate dihydrate (DCPD) conversion to HA. The size of HA crystals decreased when BMP was loaded during HA precipitation and HA immersion in BMP solution; however, it did not change when BMP was loaded during DCPD-to-HA conversion. The highest BMP uptake was achieved using the immersion method followed by HA precipitation, and the lowest via DCPD conversion. It is interesting to note that BMP loading during HA precipitation resulted in sustained and prolonged BMP release compared with the 2 other BMP loading methods. In conclusion, BMP incorporation during HA precipitation revealed itself to be the best loading method.
20
Xia, Yin, Jodie L. Babitt, Yisrael Sidis, Raymond T. Chung, and Herbert Y. Lin. "Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin." Blood 111, no. 10 (May 15, 2008): 5195–204. http://dx.doi.org/10.1182/blood-2007-09-111567.
Abstract:
Abstract Hemojuvelin (HJV) is a coreceptor for bone morphogenetic protein (BMP) signaling that regulates hepcidin expression and iron metabolism. However, the precise combinations of BMP ligands and receptors used by HJV remain unknown. HJV has also been demonstrated to bind to neogenin, but it is not known whether this interaction has a role in regulating hepcidin expression. In the present study, we show that BMP-2, BMP-4, and BMP-6 are endogenous ligands for HJV in hepatoma-derived cell lines, and that all 3 of these ligands are expressed in human liver. We demonstrate in vitro that HJV selectively uses the BMP type II receptors ActRIIA and BMPRII, but not ActRIIB, and HJV enhances utilization of ActRIIA by BMP-2 and BMP-4. Interestingly, ActRIIA is the predominant BMP type II receptor expressed in human liver. While HJV can use all 3 BMP type I receptors (ALK2, ALK3, and ALK6) in vitro, only ALK2 and ALK3 are detected in human liver. Finally, we show that HJV-induced BMP signaling and hepcidin expression are not altered by neogenin overexpression or by inhibition of endogenous neogenin expression. Thus, HJV-mediated BMP signaling and hepcidin regulation occur via a distinct subset of BMP ligands and BMP receptors, independently of neogenin.
21
Lu, Z. H., M. Ulmanen, T. S. Lindholm, P. Jalovaara, and O. Hietala. "ENDOGENOUS BMP-4 AND BMP-7 GENE EXPRESSION IN CD-1 MOUSE DURING CHONDROGENESIS INDUCED BY BOVINE BONE MORPHOGENETIC PROTEIN IMPLANTATION." Journal of Musculoskeletal Research 04, no. 03 (September 2000): 161–68. http://dx.doi.org/10.1142/s0218957700000203.
Abstract:
The osteoinductive activity of bone morphogenetic proteins can be demonstrated by implantation into the muscle pouch in the mouse to induce ectopic cartilage and bone. To study endogenous BMP expression after implantation of 2 mg of native bovine BMP, cDNA clones of the chondroinductive factors BMP-4 and BMP-7 were constructed and used as probes. The investigation concentrated on the early phase of regeneration three and seven days after implantation. Expressions of the endogenous BMP-4 and BMP-7 genes during chondrogenesis was observed. Both BMP-4 and BMP-7 genes were significantly expressed as early as seven days after implantation. The results suggest that ectopic implanted bovine BMP can induce chondrogenesis and that BMP-4/7 participated in this process. This observation could be applied clinically to the repair of damaged cartilage.
22
Ebisawa, T., K. Tada, I. Kitajima, K. Tojo, T. K. Sampath, M. Kawabata, K. Miyazono, and T. Imamura. "Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation." Journal of Cell Science 112, no. 20 (October 15, 1999): 3519–27. http://dx.doi.org/10.1242/jcs.112.20.3519.
Abstract:
Bone morphogenetic protein (BMP)-6 is a member of the transforming growth factor (TGF)-(β) superfamily, and is most similar to BMP-5, osteogenic protein (OP)-1/BMP-7, and OP-2/BMP-8. In the present study, we characterized the endogenous BMP-6 signaling pathway during osteoblast differentiation. BMP-6 strongly induced alkaline phosphatase (ALP) activity in cells of osteoblast lineage, including C2C12 cells, MC3T3-E1 cells, and ROB-C26 cells. The profile of binding of BMP-6 to type I and type II receptors was similar to that of OP-1/BMP-7 in C2C12 cells and MC3T3-E1 cells; BMP-6 strongly bound to activin receptor-like kinase (ALK)-2 (also termed ActR-I), together with type II receptors, i.e. BMP type II receptor (BMPR-II) and activin type II receptor (ActR-II). In addition, BMP-6 weakly bound to BMPR-IA (ALK-3), to which BMP-2 also bound. In contrast, binding of BMP-6 to BMPR-IB (ALK-6), and less efficiently to ALK-2 and BMPR-IA, together with BMPR-II was detected in ROB-C26 cells. Intracellular signalling was further studied using C2C12 and MC3T3-E1 cells. Among the receptor-regulated Smads activated by BMP receptors, BMP-6 strongly induced phosphorylation and nuclear accumulation of Smad5, and less efficiently those of Smad1. However, Smad8 was constitutively phosphorylated, and no further phosphorylation or nuclear accumulation of Smad8 by BMP-6 was observed. These findings indicate that in the process of differentiation to osteoblasts, BMP-6 binds to ALK-2 as well as other type I receptors, and transduces signals mainly through Smad5 and possibly through Smad1.
23
Seeherman, Howard J., Stephen P. Berasi, Christopher T. Brown, Robert X. Martinez, Z. Sean Juo, Scott Jelinsky, Michael J. Cain, et al. "A BMP/activin A chimera is superior to native BMPs and induces bone repair in nonhuman primates when delivered in a composite matrix." Science Translational Medicine 11, no. 489 (April 24, 2019): eaar4953. http://dx.doi.org/10.1126/scitranslmed.aar4953.
Abstract:
Bone morphogenetic protein (BMP)/carriers approved for orthopedic procedures achieve efficacy superior or equivalent to autograft bone. However, required supraphysiological BMP concentrations have been associated with potential local and systemic adverse events. Suboptimal BMP/receptor binding and rapid BMP release from approved carriers may contribute to these outcomes. To address these issues and improve efficacy, we engineered chimeras with increased receptor binding by substituting BMP-6 and activin A receptor binding domains into BMP-2 and optimized a carrier for chimera retention and tissue ingrowth. BV-265, a BMP-2/BMP-6/activin A chimera, demonstrated increased binding affinity to BMP receptors, including activin-like kinase-2 (ALK2) critical for bone formation in people. BV-265 increased BMP intracellular signaling, osteogenic activity, and expression of bone-related genes in murine and human cells to a greater extent than BMP-2 and was not inhibited by BMP antagonist noggin or gremlin. BV-265 induced larger ectopic bone nodules in rats compared to BMP-2 and was superior to BMP-2, BMP-2/6, and other chimeras in nonhuman primate bone repair models. A composite matrix (CM) containing calcium-deficient hydroxyapatite granules suspended in a macroporous, fenestrated, polymer mesh–reinforced recombinant human type I collagen matrix demonstrated improved BV-265 retention, minimal inflammation, and enhanced handling. BV-265/CM was efficacious in nonhuman primate bone repair models at concentrations ranging from 1/10 to 1/30 of the BMP-2/absorbable collagen sponge (ACS) concentration approved for clinical use. Initial toxicology studies were negative. These results support evaluations of BV-265/CM as an alternative to BMP-2/ACS in clinical trials for orthopedic conditions requiring augmented healing.
24
Kanzaki, Shin, Tetsu Takahashi, Takahiro Kanno, Wataru Ariyoshi, Kouhei Shinmyouzu, Toshiyuki Tujisawa, and Tatsuji Nishihara. "Heparin inhibits BMP‐2 osteogenic bioactivity by binding to both BMP‐2 and BMP receptor." Journal of Cellular Physiology 216, no. 3 (September 2008): 844–50. http://dx.doi.org/10.1002/jcp.21468.
25
Kandziora, Frank, Hermann Bail, Gerhard Schmidmaier, Georg Schollmeier, Matti Scholz, Christian Knispel, Timo Hiller, et al. "Bone morphogenetic protein—2 application by a poly(d,l-lactide)—coated interbody cage: in vivo results of a new carrier for growth factors." Journal of Neurosurgery: Spine 97, no. 1 (July 2002): 40–48. http://dx.doi.org/10.3171/spi.2002.97.1.0040.
Abstract:
Object. Growth factors such as bone morphogenetic protein—2 (BMP-2) have been proven to promote spine fusion and to overcome the disadvantages of an autologous bone graft. The optimum method to deliver such growth factors remains a matter of discussion. The purpose of this study was to determine the safety and efficacy of a new poly(d,l-lactide) (PDLLA) carrier system for BMP-2 and to compare this carrier system with a collagen sponge carrier in a sheep cervical spine interbody fusion model. Methods. Thirty-two sheep underwent C3–4 discectomy and fusion: Group 1, titanium cage (eight animals); Group 2, titanium cage coated with a PDLLA carrier (eight animals); Group 3, titanium cage coated with a PDLLA carrier including BMP-2 (150 µg) (eight animals); and Group 4, titanium cage combined with a collagen sponge carrier including BMP-2 (150 µg) (eight animals). Blood samples, body weight, and temperature were assessed. Radiographs were obtained pre- and postoperatively and after 1, 2, 4, 8, and 12 weeks. At the same time points, disc space height, intervertebral angle, and lordosis angle were measured. After the sheep were killed 12 weeks postoperatively, flexion—extension radiography was performed to evaluate fusion sites. Quantitative computerized tomography scans were obtained to assess bone mineral density (BMD), bone mineral content (BMC), and bone callus volume (BCV). Biomechanical testing was performed in flexion, extension, axial rotation, and lateral bending. Stiffness, range of motion, neutral, and elastic zone were determined. Histomorphological and -morphometrical analyses were performed, and polychrome sequential labeling was used to determine the timeframe of new bone formation. There were no differences among the groups concerning blood counts, body weight, and temperature. Compared with the noncoated cages, all PDLLA-coated cages showed significantly higher values for BMD of the callus, as well as slightly higher values for BMC, BCV, and the bone volume/total volume ratio. In comparison with the cage-alone group, the BMP-2 groups showed significantly higher values for BMD and biomechanical stiffness. Histomorphological, -morphometrical, and polychrome sequential labeling analyses demonstrated greater progression of callus formation in the BMP-2 groups than in any other group. Compared with BMP-2 delivered using a collagen sponge carrier, BMP-2 application with a PDLLA carrier resulted in a higher BCV and a greater progression of interbody callus formation in the histomorphometrical analysis. Conclusions. The use of cervical spine interbody fusion cages coated with PDLLA as a delivery system for growth factors was effective. In this 12-week follow-up study, the PDLLA coating showed no adverse effects. The slight but not significant positive effect of the PDLLA carrier on interbody fusion might be a result of the degradation process of the biodegradable carrier. Compared with collagen sponge delivery of BMP-2, the PDLLA-coated interbody cages significantly increased the results of interbody bone matrix formation. In this new combination (implant + PDLLA + growth factor) the cage represents a “real fusion” cage, because it not only serves as a mechanical device for spinal fixation but also as a local drug delivery system.
26
Bunakase, Takano, Kenta Ariga, Shimpei Miyamoto, Shin'ya Okuda, Tetsuya Tomita, Motoki Iwasaki, Kazuo Yonenobu, and Hideki Yoshikawa. "Distribution of genes for bone morphogenetic protein—4, —6, growth differentiation factor—5, and bone morphogenetic protein receptors in the process of experimental spondylosis in mice." Journal of Neurosurgery: Spine 94, no. 1 (January 2001): 68–75. http://dx.doi.org/10.3171/spi.2001.94.1.0068.
Abstract:
Object. Because little is known about the molecular mechanisms underlying the process of spondylosis, the authors examined the extent of genetic localization of several members of bone morphogenetic protein (BMP) and BMP receptors in chondrogenesis during the process of inducing spondylosis in their previously established experimental mice model. Methods. Experimental spondylosis was induced in 5-week-old ICR mice. The cervical spine was harvested chronologically, and histological sections were prepared. Messenger RNA for BMP-4, growth and differentiation (GDF)—5, BMP-6, and BMP receptors (ALK-3, -6, and BMP-RII) was localized in the tissue sections by in situ hybridization. In the early stage, BMP-4—derived mRNA was localized mainly in cells in the anterior margin of the cervical discs, together with ALK-6 and BMP-RII mRNA. No GDF-5 and BMP-6 mRNA was detected at this stage. In the late stage, cells positive for BMP-4 decreased, whereas GDF-5 and BMP-6 mRNA were localized in cells undergoing chondrogenesis. The ALK-3 mRNA began to appear in this stage, as did ALK-6 and BMP-RII. Conclusions. The localization of transcripts for BMP-4, -6, and GDF-5 as well as BMP receptors shown during the present experimental model indicate the possible involvement of molecular signaling by these BMPs in the chondrogenic progress in spondylosis.
27
Dolezal, Darin, Zhiyan Liu, Qingxiang Zhou, and Francesca Pignoni. "Fly LMBR1/LIMR-type protein Lilipod promotes germ-line stem cell self-renewal by enhancing BMP signaling." Proceedings of the National Academy of Sciences 112, no. 45 (October 28, 2015): 13928–33. http://dx.doi.org/10.1073/pnas.1509856112.
Abstract:
Limb development membrane protein-1 (LMBR1)/lipocalin-interacting membrane receptor (LIMR)-type proteins are putative nine-transmembrane receptors that are evolutionarily conserved across metazoans. However, their biological function is unknown. Here, we show that the fly family member Lilipod (Lili) is required for germ-line stem cell (GSC) self-renewal in the Drosophila ovary where it enhances bone morphogenetic protein (BMP) signaling. lili mutant GSCs are lost through differentiation, and display reduced levels of the Dpp transducer pMad and precocious activation of the master differentiation factor bam. Conversely, overexpressed Lili induces supernumerary pMad-positive bamP-GFP–negative GSCs. Interestingly, differentiation of lili mutant GSCs is bam-dependent; however, its effect on pMad is not. Thus, although it promotes stem cell self-renewal by repressing a bam-dependent process, Lilipod enhances transduction of the Dpp signal independently of its suppression of differentiation. In addition, because Lili is still required by a ligand-independent BMP receptor, its function likely occurs between receptor activation and pMad phosphorylation within the signaling cascade. This first, to our knowledge, in vivo characterization of a LMBR1/LIMR-type protein in a genetic model reveals an important role in modulating BMP signaling during the asymmetric division of an adult stem cell population and in other BMP signaling contexts.
28
Paye, Emily, René H. Germain, and Lianjun Zhang. "The formative evaluation of a forestry Best Management Practices program in a municipal watershed." Forestry Chronicle 96, no. 01 (May 2020): 61–70. http://dx.doi.org/10.5558/tfc2020-008.
Abstract:
Best Management Practices for water quality (BMPs) have been proven effective in reducing sedimentation from timber harvesting operations. Although most states in the country have BMP guidelines, many are non-regulatory, creating challenges for forest managers to ensure implementation. In surface watershed systems, BMP cost-sharing extension programs (BMP programs) are designed to encourage the implementation of BMPs. To assess the efficacy of a BMP program we examined the rates of BMP implementation on 45 properties harvested between 2013 and 2015: 22 harvests enrolled in a BMP program and 23 harvests not enrolled. We also compared our results to two previous studies completed in 2002 and 2011. Our results indicate BMP implementation was significantly better on properties participating in the BMP program. Also, BMP implementation scores improved for almost all categories evaluated when compared to the two previous studies. One BMP category with low implementation scores (even in 2018), was water diversion devices such as water bars. We suspect the BMP program is not sufficient to incentivize implementation given the time commitment for BMP implementation. Another factor at play here is that implementation may have been perceived as adequate to manage surface flow, but not optimal according to specifications dictated by the BMP field guide.
29
Shih, Hung-Yu, Chia-Wei Chang, Yi-Chieh Chen, and Yi-Chuan Cheng. "Identification of the Time Period during Which BMP Signaling Regulates Proliferation of Neural Progenitor Cells in Zebrafish." International Journal of Molecular Sciences 24, no. 2 (January 15, 2023): 1733. http://dx.doi.org/10.3390/ijms24021733.
Abstract:
Bone morphogenetic protein (BMP) signaling regulates neural induction, neuronal specification, and neuronal differentiation. However, the role of BMP signaling in neural progenitors remains unclear. This is because interruption of BMP signaling before or during neural induction causes severe effects on subsequent neural developmental processes. To examine the role of BMP signaling in the development of neural progenitors in zebrafish, we bypassed the effect of BMP signaling on neural induction and suppressed BMP signaling at different time points during gastrulation using a temporally controlled transgenic line carrying a dominant-negative form of Bmp receptor type 1aa and a chemical inhibitor of BMP signaling, DMH1. Inhibiting BMP signaling from 8 hpf could bypass BMP regulation on neural induction, induce the number of proliferating neural progenitors, and reduce the number of neuronal precursors. Inhibiting BMP signaling upregulates the expression of the Notch downstream gene hairy/E(spl)-related 2 (her2). Inhibiting Notch signaling or knocking down the Her2 function reduced neural progenitor proliferation, whereas inactivating BMP signaling in Notch-Her2 deficient background restored the number of proliferating neural progenitors. These results reveal the time window for the proliferation of neural progenitors during zebrafish development and a fine balance between BMP and Notch signaling in regulating the proliferation of neural progenitor cells.
30
Langenfeld, Elaine M., and John Langenfeld. "Bone Morphogenetic Protein-2 Stimulates Angiogenesis in Developing Tumors." Molecular Cancer Research 2, no. 3 (March 1, 2004): 141–49. http://dx.doi.org/10.1158/1541-7786.141.2.3.
Abstract:
Abstract Bone Morphogenetic Protein-2 (BMP-2) is highly overexpressed in the majority of patient-derived lung carcinomas. However, a mechanism revealing its role in cancer has not been established. Here we report that BMP-2 enhances the neovascularization of developing tumors. Recombinant BMP-2 stimulated blood vessel formation in tumors formed from A549 cells injected s.c. into thymic nude mice. Recombinant BMP-2 also enhanced angiogenesis in Matrigel plugs containing A549 cells in nude mice. The BMP-2 antagonist noggin abrogated BMP-2-induced angiogenic response. Furthermore, antisense transfection of BMP-2 cDNA resulted in a decrease in blood vessel formation in the Matrigel assays. BMP-2 induced tube formation in both human aortic endothelial cells (HAEC) and umbilical vein endothelial cells. BMP-2 also stimulated proliferation of HAEC. The ability of BMP-2 to activate endothelial cells was further demonstrated by its ability to phosphorylate Smad 1/5/8 and ERK-1/2 and to increase expression of Id1. This study reveals that BMP-2 enhanced the angiogenic response in developing tumors. Furthermore, these data suggest that BMP-2 stimulation of angiogenesis may involve the activation of endothelial cells.
31
Grabner, Gernot F., Nermeen Fawzy, Maria A. Pribasnig, Markus Trieb, Ulrike Taschler, Michael Holzer, Martina Schweiger, et al. "Metabolic disease and ABHD6 alter the circulating bis(monoacylglycerol)phosphate profile in mice and humans." Journal of Lipid Research 60, no. 5 (March 20, 2019): 1020–31. http://dx.doi.org/10.1194/jlr.m093351.
Abstract:
Bis(monoacylglycerol)phosphate (BMP) is a phospholipid that is crucial for lipid degradation and sorting in acidic organelles. Genetic and drug-induced lysosomal storage disorders (LSDs) are associated with increased BMP concentrations in tissues and in the circulation. Data on BMP in disorders other than LSDs, however, are scarce, and key enzymes regulating BMP metabolism remain elusive. Here, we demonstrate that common metabolic disorders and the intracellular BMP hydrolase α/β-hydrolase domain-containing 6 (ABHD6) affect BMP metabolism in mice and humans. In mice, dietary lipid overload strongly affects BMP concentration and FA composition in the liver and plasma, similar to what has been observed in LSDs. Notably, distinct changes in the BMP FA profile enable a clear distinction between lipid overload and drug-induced LSDs. Global deletion of ABHD6 increases circulating BMP concentrations but does not cause LSDs. In humans, nonalcoholic fatty liver disease and liver cirrhosis affect the serum BMP FA composition and concentration. Furthermore, we identified a patient with a loss-of-function mutation in the ABHD6 gene, leading to an altered circulating BMP profile. In conclusion, our results suggest that common metabolic diseases and ABHD6 affect BMP metabolism in mice and humans.
32
Mizoguchi, Takamasa, Shohei Mikami, Mari Yatou, Yui Kondo, Shuhei Omaru, Shuhei Kuwabara, Wataru Okura, et al. "Small-Molecule-Mediated Suppression of BMP Signaling by Selective Inhibition of BMP1-Dependent Chordin Cleavage." International Journal of Molecular Sciences 24, no. 5 (February 21, 2023): 4313. http://dx.doi.org/10.3390/ijms24054313.
Abstract:
BMP signaling is critical for many biological processes. Therefore, small molecules that modulate BMP signaling are useful for elucidating the function of BMP signaling and treating BMP signaling-related diseases. Here, we performed a phenotypic screening in zebrafish to examine the in vivo effects of N-substituted-2-amino-benzoic acid analogs NPL1010 and NPL3008 and found that they affect BMP signaling-dependent dorsal–ventral (D–V) patterning and bone formation in zebrafish embryos. Furthermore, NPL1010 and NPL3008 suppressed BMP signaling upstream of BMP receptors. BMP1 cleaves Chordin, an antagonist of BMP, and negatively regulates BMP signaling. Docking simulations demonstrated that NPL1010 and NPL3008 bind BMP1. We found that NPL1010 and NPL3008 partially rescued the disruptions in the D–V phenotype caused by bmp1 overexpression and selectively inhibited BMP1-dependent Chordin cleavage. Therefore, NPL1010 and NPL3008 are potentially valuable inhibitors of BMP signaling that act through selective inhibition of Chordin cleavage.
33
Huse, Kanutte, Marianne B. Eide, Christian Kersten, Erlend B. Smeland, and June H. Myklebust. "B Cell Lymphomas Are Resistant towards Bone Morphogenetic Protein (BMP) Induced Growth Inhibition." Blood 108, no. 11 (November 1, 2006): 2381. http://dx.doi.org/10.1182/blood.v108.11.2381.2381.
Abstract:
Abstract Bone morphogenetic proteins (BMPs) belong to the TGF-β superfamily, and mediate their effects mainly through the Smad signalling pathway. Whereas TGF-β is well established as one of the most potent negative regulators in hematopoietic cells, the role of BMPs remains more elusive. We have previously shown that BMP-6 inhibits the growth of naïve and memory human B cells. As high BMP-6 mRNA expression is associated with poor outcome in diffuse large B cell lymphoma (DLBCL; Rosenwald et al, N Engl J Med 2002), we hypothesized that resistance towards BMP-induced growth inhibition is a possible mechanism for lymphomagenesis. In the current study, 7 B cell lymphoma cell lines (representing Burkitt lymphoma (BL) and DLBCL) and tumour material from lymphoma patients were investigated to unravel the role of BMPs in lymphomas. We analyzed the expression of BMP receptors by FACS analysis, and found variable expression of the BMP receptor type I (Alk2, Alk3 and Alk6) and type II (BMP RII, Activin RIIA and RIIB) among the cell lines and in primary lymphoma cells, suggesting variable binding of BMPs. We next investigated the effect of BMP-2, BMP-4, BMP-6 and BMP-7 on proliferation and survival of B lymphoma cell lines, and found 2 of 7 cell lines to be resistant towards BMP-2 and BMP-4 induced growth inhibition. In contrast, 4 of 7 and 7 of 7 cell lines were resistant to BMP-6 and BMP-7 induced growth inhibition, respectively. In Sudhl6 cells that were highly sensitive to BMP-2 and BMP-6 induced apoptosis and inhibition of proliferation, we demonstrated that the cytokines IL-10, CD40 Ligand and BLyS were able to counteract the negative effects induced by BMPs, while IL-2 and IL-4 were not. On the contrary, both BMP-2 and BMP-6 greatly increased anti-IgM activation induced apoptosis. In resistant lymphoma cells, the BMPs were not able to induce detectable levels or induced low levels of phosphorylated SMAD1/5/8 compared to sensitive cell lines. Low or no increase in phosphorylation of SMAD1/5/8 induced by BMPs could only partly be explained by low/ undetectable expression of BMP receptors. Hence, upregulation of inhibitory Smads (Smad6, Smad7) or mutations in receptors or Smads represent other possible mechanisms for resistance to BMPs in lymphomas, and this is currently under investigation. We also investigated if the lymphoma cells produced BMPs themselves and found that 5 of 7 cell lines and 3 of 5 primary lymphomas produced significant amounts of BMP-7. Some lymphoma cells also had detectable levels of BMP-4 and BMP-6. Our findings that lymphoma cells are resistant towards BMP-7 and to some degree BMP-6 induced growth inhibition, whereas they produce these cytokines, suggest that resistance towards BMP induced signalling in B cell lymphomas can contribute to increased tumour growth.
34
Inagaki, Kenichi, Fumio Otsuka, Tomoko Miyoshi, Misuzu Yamashita, Mina Takahashi, Junko Goto, Jiro Suzuki, and Hirofumi Makino. "p38-Mitogen-Activated Protein Kinase Stimulated Steroidogenesis in Granulosa Cell-Oocyte Cocultures: Role of Bone Morphogenetic Proteins 2 and 4." Endocrinology 150, no. 4 (November 20, 2008): 1921–30. http://dx.doi.org/10.1210/en.2008-0851.
Abstract:
Roles of the p38-MAPK pathway in steroidogenesis were investigated using coculture of rat granulosa cells with oocytes. Activin and FSH readily phosphorylated p38 in granulosa cells. Activin effect on p38 phosphorylation was abolished by a selective activin receptor-like kinase-4, -5, and -7 inhibitor, SB431542. SB431542 decreased FSH-induced estradiol but had no effect on progesterone production with a marginal cAMP reduction, suggesting that endogenous activin is primarily involved in estradiol synthesis. FSH-induced p38 activation was not affected either by SB431542 or follistatin, suggesting that FSH activates p38 not through the endogenous activin. Bone morphogenetic protein (BMP)-2 and BMP-4 also enhanced FSH-induced p38 phosphorylation, which was augmented by oocyte action. A specific p38 inhibitor, SB203580, decreased FSH-induced estradiol production. However, FSH-induced cAMP accumulation was not changed by SB203580, suggesting that p38 activation is linked to estradiol synthesis independently of cAMP. BMP-2 and BMP-4 inhibited FSH- and forskolin (FSK)-induced progesterone and cAMP synthesis regardless of oocyte action. BMP-2, BMP-4, and activin increased FSH-induced estradiol production, which was enhanced in the presence of oocytes. In contrast to activin that enhanced FSK-induced estradiol, BMP-2 and BMP-4 had no effects on FSK-induced estradiol production, suggesting that BMP-2 and BMP-4 directly activate FSH-receptor signaling. Given that activin increased, but BMP-2 and BMP-4 decreased, FSH-induced cAMP, the effects of BMP-2 and BMP-4 on estradiol enhancement appeared to be diverged from the cAMP-protein kinase A pathway. Thus, BMP-2 and BMP-4 differentially regulate steroidogenesis by stimulating FSH-induced p38 and suppressing cAMP. The former is involved in estradiol production and enhanced by oocyte action, whereas the latter leads to reduction of progesterone synthesis.
35
Sui, Yi, Aierpati Yusufu, Kaiwei Nian, Xin Li, Wenhua Shi, Bo Cheng, and Bin Shen. "Bone Regeneration in Osteoporosis via Carbon Nanotube-Based Bone Morphogenetic Protein-2." Journal of Biomedical Nanotechnology 18, no. 7 (July 1, 2022): 1816–25. http://dx.doi.org/10.1166/jbn.2022.3399.
Abstract:
We constructed a bone morphogenetic protein 2 (BMP-2)@Carbon nanotube (CNT) delivery system to explore the feasibility of a nanodrug delivery system in the treatment of osteoporosis (OP). Osteoblasts were cultured and OP mouse models were constructed to evaluate the osteogenesis of nano-BMP-2 in OP therapy. In physicochemical property tests, we found that BMP-2 was effectively loaded into CNT to form nanoparticles (NPs) with a particle size of 100 nm. Additionally, we found that nano-BMP-2 had good stability and could effectively prolong BMP-2 release time. In cellular experiments, we found that nano-BMP-2 could penetrate osteoblasts more effectively than BMP-2 alone, and with the increase of BMP-2 loading, the amount of BMP-2 penetrating osteoblasts increased with an optimal loading of 100 μg. We determined that nano-BMP-2 could increase proliferation activity of osteoblasts to better promote OP repair. In our vivo experiments, we found that nano-BMP-2 was effectively excreted through the kidney and mainly distributed in bone tissue. Moreover, CNT effectively prolonged the half-life of BMP-2 and was safe to introduce through intramuscular injection and did not cause obvious inflammatory reactions. Following treatment, nano-BMP-2 increased body weight, femur weight, and femoral head diameter in OP mouse models. Furthermore, bone trabecular was arranged in a close and orderly fashion and was uniform in thickness in OP mice treated with nano-BMP-2. OP mice had improved bone mineral density, trabecular thickness, trabecular number, and cortical bone thickness in their metaphyseal regions, implying nano-BMP-2 treatment led to improved OP symptoms. Therefore, BMP-2@CNT may be a beneficial choice for treatment of OP.
36
Manzano-Lista, Francisco Javier, Marta Sanz-Gómez, Daniel González-Moreno, Elena Vega-Martín, Marta Gil-Ortega, Angela Schulz, Miguel Ángel Rubio, et al. "Imbalance in Bone Morphogenic Proteins 2 and 7 Is Associated with Renal and Cardiovascular Damage in Chronic Kidney Disease." International Journal of Molecular Sciences 24, no. 1 (December 20, 2022): 40. http://dx.doi.org/10.3390/ijms24010040.
Abstract:
Arterial stiffness is a major vascular complication of chronic kidney disease (CKD). The development of renal damage, hypertension, and increased pulse wave velocity (PWV) in CKD might be associated with an imbalance in bone morphogenetic proteins (BMP)-2 and BMP-7. Plasma BMP-2 and BMP-7 were determined by ELISA in CKD patients (stages I–III; n = 95) and Munich Wistar Frömter (MWF) rats. Age-matched Wistar rats were used as a control. The expression of BMP-2, BMP-7, and profibrotic and calcification factors was determined in kidney and perivascular adipose tissues (PVAT). BMP-2 was higher in stage III CKD patients compared to control subjects. BMP-7 was lower at any CKD stage compared to controls, with a significant further reduction in stage III patients. A similar imbalance was observed in MWF rats together with the increase in systolic (SBP) and diastolic blood pressure (DBP), or pulse wave velocity (PWV). MWF exhibited elevated urinary albumin excretion (UAE) and renal expression of BMP-2 or kidney damage markers, Kim-1 and Ngal, whereas renal BMP-7 was significantly lower than in Wistar rats. SBP, DBP, PWV, UAE, and plasma creatinine positively correlated with the plasma BMP-2/BMP-7 ratio. Periaortic and mesenteric PVAT from MWF rats showed an increased expression of BMP-2 and profibrotic and calcification markers compared to Wistar rats, together with a reduced BMP-7 expression. BMP-2 and BMP-7 imbalance in plasma, kidney, and PVATs is associated with vascular damage, suggesting a profibrotic/pro-calcifying propensity associated with progressive CKD. Thus, their combined analysis stratified by CKD stages might be of clinical interest to provide information about the degree of renal and vascular damage in CKD.
37
Yao, Yucheng, Medet Jumabay, Albert Ly, Melina Radparvar, Anthony H. Wang, Raushan Abdmaulen, and Kristina I. Boström. "Crossveinless 2 regulates bone morphogenetic protein 9 in human and mouse vascular endothelium." Blood 119, no. 21 (May 24, 2012): 5037–47. http://dx.doi.org/10.1182/blood-2011-10-385906.
Abstract:
Abstract The importance of morphogenetic proteins (BMPs) and their antagonists in vascular development is increasingly being recognized. BMP-4 is essential for angiogenesis and is antagonized by matrix Gla protein (MGP) and crossveinless 2 (CV2), both induced by the activin receptor like-kinase 1 (ALK1) when stimulated by BMP-9. In this study, however, we show that CV2 preferentially binds and inhibits BMP-9 thereby providing strong feedback inhibition for BMP-9/ALK1 signaling rather than for BMP-4/ALK2 signaling. CV2 disrupts complex formation involving ALK2, ALK1, BMP-4, and BMP-9 required for the induction of both BMP antagonists. It also limits VEGF expression, proliferation, and tube formation in ALK1-expressing endothelial cells. In vivo, CV2 deficiency translates into a dysregulation of vascular BMP signaling, resulting in an abnormal endothelium with increased endothelial cellularity and expression of lineage markers for mature endothelial cells. Thus, mutual regulation by BMP-9 and CV2 is essential in regulating the development of the vascular endothelium.
38
Keller, Sascha, Joachim Nickel, Jin-Li Zhang, Walter Sebald, and Thomas D. Mueller. "Molecular recognition of BMP-2 and BMP receptor IA." Nature Structural & Molecular Biology 11, no. 5 (April 4, 2004): 481–88. http://dx.doi.org/10.1038/nsmb756.
39
Barrett, Michael E. "Comparison of BMP Performance Using the International BMP Database." Journal of Irrigation and Drainage Engineering 134, no. 5 (October 2008): 556–61. http://dx.doi.org/10.1061/(asce)0733-9437(2008)134:5(556).
40
Yilgor, P., N. Hasirci, and V. Hasirci. "Sequential BMP-2/BMP-7 delivery from polyester nanocapsules." Journal of Biomedical Materials Research Part A 9999A (2009): NA. http://dx.doi.org/10.1002/jbm.a.32520.
41
Ji, Tuo, Hidehiko Takabayashi, Maria Mao, Xu Han, Xiang Xue, Jennifer C. Brazil, Kathryn A. Eaton, Yatrik M. Shah, and Andrea Todisco. "Regulation and function of bone morphogenetic protein signaling in colonic injury and inflammation." American Journal of Physiology-Gastrointestinal and Liver Physiology 312, no. 1 (January 1, 2017): G24—G33. http://dx.doi.org/10.1152/ajpgi.00169.2016.
Abstract:
The bone morphogenetic proteins (BMPs) regulate gastrointestinal homeostasis. We investigated the expression of BMP-4 and the localization and function of BMP signaling during colonic injury and inflammation. Mice expressing the β-galactosidase ( β-gal) gene under the control of a BMP-responsive element (BRE), BMP-4-β-gal/ mice, and animals generated by crossing villin-Cre mice to mice with floxed alleles of BMP receptor 1A ( villin-Cre;Bmpr1a flox/flox) were treated with dextran sodium sulfate (DSS) to induce colonic injury and inflammation. Expression of BMP-4, β-gal, BMPR1A, IL-8, α-smooth muscle actin, and phosphorylated Smad1, -5, and -8 was assessed by X-Gal staining, quantitative RT-PCR, and immunohistochemistry. Morphology of the colonic mucosa was examined by staining with hematoxylin and eosin. The effect of IFN-γ, TNF-α, IL-1β, and IL-6 on BMP-4 mRNA expression was investigated in human intestinal fibroblasts, whereas that of BMP-4 on IL-8 was assessed in human colonic organoids. BMP-4 was localized in α-smooth muscle actin-positive mesenchymal cells while the majority of BMP-generated signals targeted the epithelium. DSS caused injury and inflammation leading to reduced expression of BMP-4 and of BMPR1A mRNAs, and to decreased BMP signaling. Deletion of BMPR1A enhanced colonic inflammation and damage. Administration of anti-TNF-α antibodies to DSS-treated mice ameliorated colonic inflammation and increased the expression of BMP-4 and BMPR1A mRNAs. TNF-α and IL-1β inhibited both basal and IFN-γ-stimulated BMP-4 expression, whereas IL-6 had no effect. BMP-4 reduced TNF-α-stimulated IL-8 mRNA expressor IL-8 mRNA expression in the organoids. Inflammation and injury inhibit BMP-4 expression and signaling, leading to enhanced colonic damage and inflammation. These observations underscore the importance of BMP signaling in the regulation of intestinal inflammation and homeostasis. NEW & NOTEWORTHY In this study we report a series of novel observations that underscore the importance of bone morphogenetic protein (BMP) signaling in the regulation of colonic homeostasis during the development of injury and inflammation. In particular, we present evidence that BMP signaling mitigates the response of the colonic epithelium to injury and inflammation and that cytokines, such as TNF-α and IL-1β, inhibit the expression of BMP-4.
42
Erickson, GF, L. Fuqua, and S. Shimasaki. "Analysis of spatial and temporal expression patterns of bone morphogenetic protein family members in the rat uterus over the estrous cycle." Journal of Endocrinology 182, no. 2 (August 1, 2004): 203–17. http://dx.doi.org/10.1677/joe.0.1820203.
Abstract:
Recent studies have demonstrated that bone morphogenetic proteins (BMPs) play fundamental roles in female fertility. This is particularly evident in terms of the ovary. One major question that is just beginning to be addressed is the role of BMPs in the non-pregnant uterus. To help fill this gap, we used in situ hybridization to investigate the expression of BMP family members in the rat uterus over the estrous cycle. We found that the endometrial/uterine cycle is accompanied by the expression of several components of the BMP pathway - including ligands, receptors and antagonists. The mRNAs encoding BMP receptors are expressed in the epithelial (BMP-RIA, -RIB and -RII), periluminal stroma (BMP-RIA and -RII) and smooth muscle cells (BMP-RIA and -RII). The expression of all three receptors showed clear cyclic variations. The mRNAs encoding BMP ligands were highly expressed in the periluminal stroma (BMP-2 and -7) and glandular epithelium (BMP-7). The expression of BMP-2, but not BMP-7, was cyclical. Notably, the periluminal stroma expressed noggin mRNA. In the blood vascular system, BMP-4, -6 and -RII mRNAs were expressed in myometrial endothelial cells. Interestingly, follistatin, noggin, and BMP-4, -6 and -7 mRNAs were expressed in eosinophilic leukocytes, suggesting unexpected roles for eosinophil-derived BMPs in uterine function. We conclude that BMP ligands, receptors and antagonists are expressed in spatially and temporally restricted patterns that are consistent with a physiological role for these regulatory molecules in promoting uterine cellular processes including cell proliferation, differentiation and apoptosis during the cycle.
43
Au, Jennie, Daniela F. Requena, Hannah Rishik, Sampada Kallol, Chandana Tekkatte, Omar A. Farah, Ryan Kittle, Morgan Meads, Anna Wakeland, and Francesca Soncin. "Role of autocrine bone morphogenetic protein signaling in trophoblast stem cells." Biology of Reproduction 106, no. 3 (November 15, 2021): 540–50. http://dx.doi.org/10.1093/biolre/ioab213.
Abstract:
Abstract The Bone Morphogenetic Protein (BMP) pathway is involved in numerous developmental processes, including cell growth, apoptosis, and differentiation. In mouse embryogenesis, BMP signaling is a well-known morphogen for both mesoderm induction and germ cell development. Recent evidence points to a potential role in development of the extraembryonic compartment, including trophectoderm-derived tissues. In this study, we investigated the effect of BMP signaling in both mouse and human trophoblast stem cells (TSC) in vitro, evaluating the expression and activation of the BMP signaling response machinery, and the effect of BMP signaling manipulation during TSC maintenance and differentiation. Both mouse trophoblast stem cells (mTSC) and human trophoblast stem cells (hTSC) expressed various BMP ligands and the receptors BMPR1A and BMPR2, necessary for BMP response, and displayed maximal active BMP signaling when undifferentiated. We also observed a conserved modulatory role of BMP signaling during trophoblast differentiation, whereby maintenance of active BMP signaling blunted differentiation of TSC in both species. Conversely, the effect of BMP signaling on the undifferentiated state of TSC appeared to be species-specific, with SMAD-independent signaling important in maintenance of mTSC, and a more subtle role for both SMAD-dependent and -independent BMP signaling in hTSC. Altogether, these data establish an autocrine role for the BMP pathway in the trophoblast compartment. As specification and correct differentiation of the extraembryonic compartment are fundamental for implantation and early placental development, insights on the role of the BMP signaling in early development might prove useful in the setting of in vitro fertilization as well as targeting trophoblast-associated placental dysfunction.
44
Wordinger, Robert J., and Abbot F. Clark. "Bone Morphogenetic Proteins and Their Receptors in the Eye." Experimental Biology and Medicine 232, no. 8 (September 2007): 979–92. http://dx.doi.org/10.3181/0510-mr-345.
Abstract:
The human genome encodes at least 42 different members of the transforming growth factor-β superfamily of growth factors. Bone morphogenetic proteins (BMPs) are the largest subfamily of proteins within the transforming growth factor-β superfamily and are involved in numerous cellular functions including development, morphogenesis, cell proliferation, apoptosis, and extracellular matrix synthesis. This article first reviews BMPs and BMP receptors, BMP signaling pathways, and mechanisms controlling BMP signaling. Second, we review BMP and BMP receptor expression during embryonic ocular development/ differentiation and in adult ocular tissues. Lastly, future research directions with respect to BMP, BMP receptors, and ocular tissues are suggested.
45
Caperuto, Luciana Chagas, Gabriel Forato Anhê, Tavane David Cambiaghi, Eliana Hiromi Akamine, Daniella do Carmo Buonfiglio, José Cipolla-Neto, Rui Curi, and Silvana Bordin. "Modulation of Bone Morphogenetic Protein-9 Expression and Processing by Insulin, Glucose, and Glucocorticoids: Possible Candidate for Hepatic Insulin-Sensitizing Substance." Endocrinology 149, no. 12 (August 14, 2008): 6326–35. http://dx.doi.org/10.1210/en.2008-0655.
Abstract:
Bone morphogenetic protein 9 (BMP-9), a member of the TGF-β superfamily predominantly expressed in nonparenchymal liver cells, has been demonstrated to improve glucose homeostasis in diabetic mice. Along with this therapeutic effect, BMP-9 was proposed as a candidate for the hepatic insulin-sensitizing substance (HISS). Whether BMP-9 plays a physiological role in glucose homeostasis is still unknown. In the present study, we show that BMP-9 expression and processing is severely reduced in the liver of insulin-resistant rats. BMP-9 expression and processing was directly stimulated by in situ exposition of the liver to the combination of glucose and insulin and oral glucose in overnight fasted rats. Additionally, prolonged fasting (72 h) abrogated refeeding-induced BMP-9 expression and processing. Previous exposition to dexamethasone, a known inductor of insulin resistance, reduced BMP-9 processing stimulated by the combination of insulin and glucose. Finally, we show that neutralization of BMP-9 with an anti-BMP-9 antibody induces glucose intolerance and insulin resistance in 12-h fasted rats. Collectively, the present results demonstrate that BMP-9 plays an important role in the control of glucose homeostasis of the normal rat. Additionally, BMP-9 is expressed and processed in an HISS-like fashion, which is impaired in the presence of insulin resistance. BMP-9 regulation according to the feeding status and the presence of diabetogenic factors reinforces the hypothesis that BMP-9 might exert the role of HISS in glucose homeostasis physiology.
46
Wang, Fei, Hongfang Wei, Chengdong Hu, Dongfeng Li, Xiwei Huo, Rui Wang, and Haitao Li. "Experimental Study on Construction of Tissue Engineered Bone by Autologous Oxygen Release Nano-Bionic Scaffold Combined with Bone Morphogenetic Protein-2 Induced Bone Marrow Mesenchymal Stem Cells." Journal of Biomaterials and Tissue Engineering 9, no. 9 (September 1, 2019): 1254–60. http://dx.doi.org/10.1166/jbt.2019.2120.
Abstract:
Bone marrow mesenchymal stem cells (BMSCs) are used for bone tissue engineering. BMP-2 and autologous oxygen-releasing nano-bionic scaffolds promote bone differentiation of BMSCs. Our study intends to evaluate the role of autologous oxygen-releasing nano-bionic scaffolds combined with BMP-2-induced BMSCs in the construction of tissue engineered bone. Rat BMSCs were isolated and transfected with NC (negative control group) and BMP-2 (BMP-2 plasmid group), respectively. Healthy male SD rats were randomly and equally divided into fracture group, negative control group and the BMP-2 group which was implanted with autologous oxygen-releasing nano-bionic scaffolds to synthesize BMSCs and transfected with BMP-2 plasmids respectively followed by analysis of osteophytes growth, ALP activity, expression of BMP-2, type II collagen, Runx2 and OC by real time PCR, TGF-β1 secretion by ELISA and BMP-2 protein expression by western blot. BMSCs induced by autologous oxygen release nano-bionic scaffold combined with BMP-2 can significantly promote the increase of bone mineral density, increase the expression of Runx2 and OC, promote ALP activity, upregulate type II collagen, BMP-2 mRNA and protein, and TGF-β1 secretion compared to fracture group (P < 0.05). The BMSCs induced by autologous oxygen-releasing nanobionic scaffolds transfected with BMP-2 had a more significant effect on bone repair. Autologous oxygen-releasing nano-bionic scaffolds combined with BMP-2-induced BMSCs can promote bone healing by regulating BMP-2 and increasing osteogenesis at the bone defect.
47
Herhaus, Lina, Mazin A. Al-Salihi, Kevin S. Dingwell, Timothy D. Cummins, Lize Wasmus, Janis Vogt, Richard Ewan, et al. "USP15 targets ALK3/BMPR1A for deubiquitylation to enhance bone morphogenetic protein signalling." Open Biology 4, no. 5 (May 2014): 140065. http://dx.doi.org/10.1098/rsob.140065.
Abstract:
Protein kinase ALK3/BMPR1A mediates bone morphogenetic protein (BMP) signalling through phosphorylation and activation of SMADs 1/5/8. SMAD6, a transcriptional target of BMP, negatively regulates the BMP pathway by recruiting E3 ubiquitin ligases and targeting ALK3 for ubiquitin-mediated degradation. Here, we identify a deubiquitylating enzyme USP15 as an interactor of SMAD6 and ALK3. We show that USP15 enhances BMP-induced phosphorylation of SMAD1 by interacting with and deubiquitylating ALK3. RNAi -mediated depletion of USP15 increases ALK3 K48-linked polyubiquitylation, and reduces both BMP-induced SMAD1 phosphorylation and transcription of BMP target genes. We also show that loss of USP15 expression from mouse myoblast cells inhibits BMP-induced osteoblast differentiation. Furthermore, USP15 modulates BMP-induced phosphorylation of SMAD1 and transcription during Xenopus embryogenesis.
48
Vukicevic, S., M. N. Helder, and F. P. Luyten. "Developing human lung and kidney are major sites for synthesis of bone morphogenetic protein-3 (osteogenin)." Journal of Histochemistry & Cytochemistry 42, no. 7 (July 1994): 869–75. http://dx.doi.org/10.1177/42.7.8014470.
Abstract:
Bone morphogenetic protein-3 (BMP-3; osteogenin) is a member of the transforming growth factor-beta superfamily. We used human BMP-3 cDNA probes and a specific BMP-3 polyclonal peptide antibody to analyze BMP-3 expression and synthesis in human fetal and adult tissues. Northern blot hybridization revealed two mRNA species of 7 and 3 KB. High levels of BMP-3 mRNA were found in fetal lungs. By in situ hybridization, the BMP-3 transcripts were found in lung bronchial epithelium, straight collecting kidney tubules, intestinal mucosa, perichondrium, periosteum, and osteoblasts of human embryos of 6-14 weeks' gestation. Cellular BMP-3 immunostaining co-localized with the distribution of RNA. In addition, bone matrix showed intensive BMP-3 staining. These data suggest that although BMP-3 has been isolated from bone matrix, it may have additional regulatory roles in the morphogenesis and/or function of human lung, kidney, and intestine.
49
Xiao, Han, Yang Chen, Muzhi Li, Qiang Shi, Yan Xu, Jianzhong Hu, Xing Li, Can Chen, and Hongbin Lu. "Cell-Free Book-Shaped Decellularized Tendon Matrix Graft Capable of Controlled Release of BMP-12 to Improve Tendon Healing in a Rat Model." American Journal of Sports Medicine 49, no. 5 (March 5, 2021): 1333–47. http://dx.doi.org/10.1177/0363546521994555.
Abstract:
Background: Achilles tendon (AT) defects often occur in traumatic and chronic injuries. Currently, no graft can satisfactorily regenerate parallel tendinous tissue at the defect site to completely restore AT function. Purpose: To develop a cell-free functional graft by tethering bone morphogenetic protein 12 (BMP-12) on a book-shaped decellularized tendon matrix (BDTM) and to determine whether this graft is more beneficial for AT defect healing than an autograft. Study Design: Controlled laboratory study. Methods: Canine patellar tendon was sectioned into a book shape and decellularized to fabricate a BDTM. The collagen-binding domain (CBD) was fused into the N-terminus of BMP-12 to synthesize a recombinant BMP-12 (CBD-BMP-12), which was tethered to the BDTM to prepare a cell-free functional graft (CBD-BMP-12/BDTM). After its tensile resistance, tenogenic inducibility, and BMP-12 release dynamics were evaluated, the efficacy of the graft for tendon regeneration was determined in a rat model. A total of 140 mature male Sprague-Dawley rats underwent AT tenotomy. The defect was reconstructed with reversed AT (autograft group), native BMP-12 tethered to an intact decellularized tendon matrix (IDTM; NAT-BMP-12/IDTM group), native BMP-12 tethered to a BDTM (NAT-BMP-12/BDTM group), CBD-BMP-12 tethered on an IDTM (CBD-BMP-12/IDTM group), and CBD-BMP-12 tethered on a BDTM (CBD-BMP-12/BDTM group). The rats were sacrificed 4 or 8 weeks after surgery to harvest AT specimens. Six specimens from each group at each time point were used for histological evaluation; the remaining 8 specimens were used for biomechanical testing. Results: In vitro CBD-BMP-12/BDTM was noncytotoxic, showed high biomimetics with native tendons, was suitable for cell adhesion and growth, and had superior tenogenic inducibility. In vivo the defective AT in the CBD-BMP-12/BDTM group regenerated more naturally than in the other groups, as indicated by more spindle-shaped fibroblasts embedded in a matrix of parallel fibers. The biomechanical properties of the regenerated AT in the CBD-BMP-12/BDTM group also increased more significantly than in the other groups. Conclusion: CBD-BMP-12/BDTM is more beneficial than autograft for healing AT defects in a rat model. Clinical Relevance: The findings of this study demonstrate that CBD-BMP-12/BDTM can serve as a practical graft for reconstructing AT defects.
50
Greenfeld, Hannah, Jerome Lin, and Mary C. Mullins. "The BMP signaling gradient is interpreted through concentration thresholds in dorsal–ventral axial patterning." PLOS Biology 19, no. 1 (January 22, 2021): e3001059. http://dx.doi.org/10.1371/journal.pbio.3001059.
Abstract:
Bone Morphogenetic Protein (BMP) patterns the dorsal–ventral (DV) embryonic axis in all vertebrates, but it is unknown how cells along the DV axis interpret and translate the gradient of BMP signaling into differential gene activation that will give rise to distinct cell fates. To determine the mechanism of BMP morphogen interpretation in the zebrafish gastrula, we identified 57 genes that are directly activated by BMP signaling. By using Seurat analysis of single-cell RNA sequencing (scRNA-seq) data, we found that these genes are expressed in at least 3 distinct DV domains of the embryo. We distinguished between 3 models of BMP signal interpretation in which cells activate distinct gene expression through interpretation of thresholds of (1) the BMP signaling gradient slope; (2) the BMP signal duration; or (3) the level of BMP signal activation. We tested these 3 models using quantitative measurements of phosphorylated Smad5 (pSmad5) and by examining the spatial relationship between BMP signaling and activation of different target genes at single-cell resolution across the embryo. We found that BMP signaling gradient slope or BMP exposure duration did not account for the differential target gene expression domains. Instead, we show that cells respond to 3 distinct levels of BMP signaling activity to activate and position target gene expression. Together, we demonstrate that distinct pSmad5 threshold levels activate spatially distinct target genes to pattern the DV axis.