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Journal articles on the topic 'Osteoclast'

Author: Grafiati

Published: 4 June 2021

Last updated: 25 July 2025

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1

Yu, Anna Xiao-Dan, Jian Xiao, Shi-Zheng Zhao, et al. "Biological Evaluation and Transcriptomic Analysis of Corylin as an Inhibitor of Osteoclast Differentiation." International Journal of Molecular Sciences 22, no. 7 (2021): 3540. http://dx.doi.org/10.3390/ijms22073540.

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Corylin, a flavonoid isolated from the fruit of Psoralea corylifolia, has an osteogenic effect on osteoblasts in vitro and bone micromass ex vivo. However, the effect and mechanism of corylin in regulating osteoclastogenesis remain unknown. By using murine bone marrow macrophages as the osteoclast precursor, corylin was found to inhibit the receptor activator of nuclear factor (NF) κB ligand (RANKL)-induced osteoclast differentiation via down-regulating osteoclastic marker genes. In parallel, F-actin formation and osteoclast migration were diminished in corylin-treated cultured osteoclasts, an

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Alatalo, Sari L., Jussi M. Halleen, Teuvo A. Hentunen, Jukka Mönkkönen, and H. Kalervo Väänänen. "Rapid Screening Method for Osteoclast Differentiation in Vitro That Measures Tartrate-resistant Acid Phosphatase 5b Activity Secreted into the Culture Medium." Clinical Chemistry 46, no. 11 (2000): 1751–54. http://dx.doi.org/10.1093/clinchem/46.11.1751.

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Abstract Background: Osteoclasts secrete tartrate-resistant acid phosphatase (TRAP; EC 3.1.3.2) 5b into the circulation. We studied the release of TRAP 5b from osteoclasts using a mouse in vitro osteoclast differentiation assay. Methods: We developed and characterized a polyclonal antiserum in rabbits, using purified human osteoclastic TRAP 5b as antigen. The antiserum was specific for TRAP in Western analysis of mouse osteoclast culture medium and was used to develop an immunoassay. We cultured mouse bone marrow-derived osteoclast precursor cells for 3–7 days with or without clodronate in the

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3

Combs, Charlotte E., Karen Fuller, Hashethra Kumar, et al. "Urocortin is a novel regulator of osteoclast differentiation and function through inhibition of a canonical transient receptor potential 1-like cation channel." Journal of Endocrinology 212, no. 2 (2011): 187–97. http://dx.doi.org/10.1530/joe-11-0254.

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This study investigated the role of urocortin (UCN), a member of the corticotrophin-releasing factor (CRF) family of peptides, in osteoclast maturation and function. We found that 10−7 M UCN significantly (P<0.05) suppressed osteoclast differentiation from bone marrow precursor cells in culture and reduced the expression of several osteoclastic markers. Furthermore, UCN potently suppressed osteoclast bone resorption, by significantly inhibiting both the plan area of bone resorbed by osteoclasts and actin ring formation within osteoclasts at 10−9 M (P<0.05), with complete inhibition at 10

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Fong, E. L. S., E. L. Prabha, and T. Carney. "POS0348 DEVELOPING A WHOLE MOUNT FLUORESCENT OSTEOCLAST ACTIVITY ASSAY USING THE ELF97 PHOSPHATASE SUBSTRATE TO VISUALISE AND QUANTIFY IN SITU OSTEOCLAST ACTIVITY IN ZEBRAFISH (DANIO RERIO)." Annals of the Rheumatic Diseases 81, Suppl 1 (2022): 427.3–428. http://dx.doi.org/10.1136/annrheumdis-2022-eular.5402.

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BackgroundOsteoporosis is a mineral bone disease arising from the predominance of osteoclastic bone resorption. Bisphosphonates which inhibit osteoclasts are commonly used in osteoporosis treatment, but are not without severe adverse effects like osteonecrosis of the jaw. The mechanisms behind the development of such phenomena is not well understood. Bone homeostasis is achieved through an intimate cross-talk between osteoclasts and osteoblasts. Thus, it is important to visualise activities of these cells simultaneously in situ. Currently, there are means to visualise osteoclast shape and numb

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Niida, Shumpei, Masato Kaku, Hitoshi Amano, et al. "Vascular Endothelial Growth Factor Can Substitute for Macrophage Colony-Stimulating Factor in the Support of Osteoclastic Bone Resorption." Journal of Experimental Medicine 190, no. 2 (1999): 293–98. http://dx.doi.org/10.1084/jem.190.2.293.

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We demonstrated previously that a single injection of recombinant human macrophage colony-stimulating factor (rhM-CSF) is sufficient for osteoclast recruitment and survival in osteopetrotic (op/op) mice with a deficiency in osteoclasts resulting from a mutation in M-CSF gene. In this study, we show that a single injection of recombinant human vascular endothelial growth factor (rhVEGF) can similarly induce osteoclast recruitment in op/op mice. Osteoclasts predominantly expressed VEGF receptor 1 (VEGFR-1), and activity of recombinant human placenta growth factor 1 on osteoclast recruitment was

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Moreaux, Jerome, Dirk Hose, Alboukadel Kassambara, et al. "Osteoclast-gene expression profiling reveals osteoclast-derived CCR2 chemokines promoting myeloma cell migration." Blood 117, no. 4 (2011): 1280–90. http://dx.doi.org/10.1182/blood-2010-04-279760.

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Abstract Multiple myeloma is characterized by the clonal expansion of malignant plasma cells (multiple myeloma cells [MMCs]), in the bone marrow. Osteolytic bone lesions are detected in 80% of patients because of increased osteoclastic bone resorption and reduced osteoblastic bone formation. MMCs are found closely associated with sites of increased bone resorption. Osteoclasts strongly support MMC survival in vitro. To further elucidate the mechanisms involved in osteoclast/MMC interaction, we have identified 552 genes overexpressed in osteoclasts compared with other bone marrow cell subpopula

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Fuller, K., J. M. Owens, and T. J. Chambers. "Macrophage inflammatory protein-1 alpha and IL-8 stimulate the motility but suppress the resorption of isolated rat osteoclasts." Journal of Immunology 154, no. 11 (1995): 6065–72. http://dx.doi.org/10.4049/jimmunol.154.11.6065.

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Abstract Cells of the osteoblastic lineage play a major role in the regulation of osteoclastic bone resorption. Recent studies have demonstrated production of chemokines by osteoblastic cells. Although these phagocyte-stimulating and proinflammatory cytokines act as chemoattractants and activators for other members of the hemopoietic lineage, their actions on osteoclasts have not been characterized. We found that macrophage inflammatory protein-1 alpha (MIP-1 alpha) and IL-8 inhibited bone resorption by rat osteoclasts, primarily through reduction in the proportion of osteoclasts resorbing bon

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8

Perkins, S. L., and S. J. Kling. "Local concentrations of macrophage colony-stimulating factor mediate osteoclastic differentiation." American Journal of Physiology-Endocrinology and Metabolism 269, no. 6 (1995): E1024—E1030. http://dx.doi.org/10.1152/ajpendo.1995.269.6.e1024.

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Macrophage colony-stimulating factor (M-CSF) is essential for differentiation of osteoclasts and macrophages from a common bone marrow precursor. Using ST-2 stromal cell/murine bone marrow coculture, we studied the effects of increasing amounts of M-CSF on differentiation of macrophages and osteoclasts. Addition of exogenous M-CSF caused a dose-dependent 98% decrease in tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells, accompanied by a 2.5-fold increase in nonspecific esterase-staining macrophages. Similar decrease in osteoclastic functional activity, including 125I-lab

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9

Cheng, Yin, Haixia Liu, Jing Li, et al. "Evaluation of culture conditions for osteoclastogenesis in RAW264.7 cells." PLOS ONE 17, no. 11 (2022): e0277871. http://dx.doi.org/10.1371/journal.pone.0277871.

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Osteoclasts are the only multinucleated cells in vivo responsible for bone resorption and are vital for regulating bone remodeling and maintaining bone mass. The RAW264.7 cell line is widely used to study osteoclastic differentiation and biological molecular mechanism. However, protocols for inducing osteoclast formation in RAW264.7 cells vary considerably between laboratories, hindering the replication of results. Therefore, we tested the influence of culture conditions on osteoclast differentiation, including cell density and receptor activator of nuclear factor kappa-B ligand (RANKL) concen

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Kameda, Takashi, Hiroshi Mano, Tatsuhisa Yuasa, et al. "Estrogen Inhibits Bone Resorption by Directly Inducing Apoptosis of the Bone-resorbing Osteoclasts." Journal of Experimental Medicine 186, no. 4 (1997): 489–95. http://dx.doi.org/10.1084/jem.186.4.489.

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Estrogen deficiency causes bone loss, which can be prevented by estrogen replacement therapy. Using a recently developed technique for isolation of highly purified mammalian osteoclasts, we showed that 17 β-estradiol (E2) was able to directly inhibit osteoclastic bone resorption. At concentrations effective for inhibiting bone resorption, E2 also directly induced osteoclast apoptosis in a dose- and time-dependent manner. ICI164,384 and tamoxifen, as pure and partial antagonists, respectively, completely or partially blocked the effect of E2 on both inhibition of osteoclastic bone resorption an

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Lerner, Ulf H. "New Molecules in the Tumor Necrosis Factor Ligand and Receptor Superfamilies with Importance for Physiological and Pathological Bone Resorption." Critical Reviews in Oral Biology & Medicine 15, no. 2 (2004): 64–81. http://dx.doi.org/10.1177/154411130401500202.

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Osteoclasts are tissue-specific polykaryon bone-resorbing cells derived from the monocyte/macrophage hematopoietic lineage with specialized functions required for the adhesion of the cells to bone and the subsequent polarization of the cell membrane, secretion of acid to dissolve mineral crystals, and release of proteolytic enzymes to degrade the extracellular matrix proteins. Most pathological conditions in the skeleton lead to loss of bone due to excess osteoclastic bone resorption, including periodontal disease, rheumatoid arthritis, and osteoporosis. In rare cases, most of them genetic, pa

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Blair, H. C., S. L. Teitelbaum, L. E. Grosso, et al. "Extracellular-matrix degradation at acid pH. Avian osteoclast acid collagenase isolation and characterization." Biochemical Journal 290, no. 3 (1993): 873–84. http://dx.doi.org/10.1042/bj2900873.

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Osteoclasts degrade bone matrix, which is mainly type I collagen and hydroxyapatite, in an acidic extracellular compartment. Thus we reasoned that osteoclasts must produce an acid collagenase. We purified this enzyme, a 31 kDa protein, from avian osteoclast lysates (in 100 mM acetate/1 mM CHAPS/1 mM dithiothreitol, pH 4.4), fractionated by (NH2)2SO4 precipitation, gelatin-affinity, cation exchange, and gel filtration. Fraction activity was measured using diazotized collagen or 3H-labelled cross-linked collagen (decalcified and trypsin-treated metabolically L-[4,5-3H]proline-labelled bone) as s

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Martin-Millan, Marta, Maria Almeida, Elena Ambrogini та ін. "The Estrogen Receptor-α in Osteoclasts Mediates the Protective Effects of Estrogens on Cancellous But Not Cortical Bone". Molecular Endocrinology 24, № 2 (2010): 323–34. http://dx.doi.org/10.1210/me.2009-0354.

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Abstract Estrogens attenuate osteoclastogenesis and stimulate osteoclast apoptosis, but the molecular mechanism and contribution of these effects to the overall antiosteoporotic efficacy of estrogens remain controversial. We selectively deleted the estrogen receptor (ER)α from the monocyte/macrophage cell lineage in mice (ERαLysM−/−) and found a 2-fold increase in osteoclast progenitors in the marrow and the number of osteoclasts in cancellous bone, along with a decrease in cancellous bone mass. After loss of estrogens these mice failed to exhibit the expected increase in osteoclast progenitor

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Møller, Anaïs M. J., Jean-Marie Delaissé, Jacob B. Olesen, et al. "Fusion Potential of Human Osteoclasts In Vitro Reflects Age, Menopause, and In Vivo Bone Resorption Levels of Their Donors—A Possible Involvement of DC-STAMP." International Journal of Molecular Sciences 21, no. 17 (2020): 6368. http://dx.doi.org/10.3390/ijms21176368.

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It is well established that multinucleation is central for osteoclastic bone resorption. However, our knowledge on the mechanisms regulating how many nuclei an osteoclast will have is limited. The objective of this study was to investigate donor-related variations in the fusion potential of in vitro-generated osteoclasts. Therefore, CD14+ monocytes were isolated from 49 healthy female donors. Donor demographics were compared to the in vivo bone biomarker levels and their monocytes’ ability to differentiate into osteoclasts, showing that: (1) C-terminal telopeptide of type I collagen (CTX) and

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Klein-Nulend, J., M. A. van Duin, T. P. Green, V. Everts, and T. J. de Vries. "The dual specific Src/Abl kinase inhibitor AZD0530 inhibits the formation and activity of human osteoclasts." Journal of Clinical Oncology 25, no. 18_suppl (2007): 3602. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.3602.

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3602 Background: Gene knockout studies have demonstrated the critical importance of the non-receptor TK Src to osteoclast bone resorptive function. Deregulated Src TK activity is also reported as a hallmark of the invasive cancer cell. Bone metastatic cancer cells interact with and activate osteoclasts in a destructive cycle of bone degradation and stimulation of tumor cell growth. Therefore targeting Src activity would appear to be a rational therapeutic approach in treating metastatic bone disease. We have reported previously (AACR 2005) on the activity of the dual Src/Abl kinase inhibitor A

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Lee, Kyunghee, Incheol Seo, Mun Choi, and Daewon Jeong. "Roles of Mitogen-Activated Protein Kinases in Osteoclast Biology." International Journal of Molecular Sciences 19, no. 10 (2018): 3004. http://dx.doi.org/10.3390/ijms19103004.

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Bone undergoes continuous remodeling, which is homeostatically regulated by concerted communication between bone-forming osteoblasts and bone-degrading osteoclasts. Multinucleated giant osteoclasts are the only specialized cells that degrade or resorb the organic and inorganic bone components. They secrete proteases (e.g., cathepsin K) that degrade the organic collagenous matrix and establish localized acidosis at the bone-resorbing site through proton-pumping to facilitate the dissolution of inorganic mineral. Osteoporosis, the most common bone disease, is caused by excessive bone resorption,

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Huang, W. H., L. L. Daniels, D. J. Wood, U. Seydel, J. M. Papadimitriou, and M. H. Zheng. "VITAMIN D RECEPTOR mRNA IS EXPRESSED IN OSTEOCLAST-LIKE CELLS OF HUMAN GIANT CELL TUMOR OF BONE (OSTEOCLASTOMA)." Journal of Musculoskeletal Research 03, no. 03 (1999): 201–7. http://dx.doi.org/10.1142/s021895779900021x.

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The conventional view of the effects of 1,25- (OH)2D3 on osteoclastogenesis and bone resorption are thought to be mediated by stromal cells or osteoblastic cell. Giant cell tumor of bone (GCT) is characterized by multinuclear giant cells (osteoclast-like cells) distributed among a mass of mononuclear cells. Because it is very difficult to obtain normal human osteoclasts, many investigators, including ourselves, have used GCT as a source of human osteoclasts to enhance the understanding of normal skeletal remodeling and especially the hormone regulation of osteoclast functions. In this report,

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Nakamura, I., M. F. Pilkington, P. T. Lakkakorpi, et al. "Role of alpha(v)beta(3) integrin in osteoclast migration and formation of the sealing zone." Journal of Cell Science 112, no. 22 (1999): 3985–93. http://dx.doi.org/10.1242/jcs.112.22.3985.

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The alpha(v)beta(3) integrin is abundantly expressed in osteoclasts and has been implicated in the regulation of osteoclast function, especially in cell attachment. However, in vivo studies have shown that echistatin, an RGD-containing disintegrin which binds to alpha(v)beta(3), inhibits bone resorption without changing the number of osteoclasts on the bone surface, suggesting inhibition of osteoclast activity. The objective of this study was to examine how occupancy of alpha(v)beta(3) integrins inhibits osteoclast function, using primary rat osteoclasts and murine pre-fusion osteoclast-like c

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Ewanchuk, Benjamin W., Corey R. Arnold, Dale R. Balce та ін. "A non-immunological role for γ-interferon–inducible lysosomal thiol reductase (GILT) in osteoclastic bone resorption". Science Advances 7, № 17 (2021): eabd3684. http://dx.doi.org/10.1126/sciadv.abd3684.

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The extracellular bone resorbing lacuna of the osteoclast shares many characteristics with the degradative lysosome of antigen-presenting cells. γ-Interferon–inducible lysosomal thiol reductase (GILT) enhances antigen processing within lysosomes through direct reduction of antigen disulfides and maintenance of cysteine protease activity. In this study, we found the osteoclastogenic cytokine RANKL drove expression of GILT in osteoclast precursors in a STAT1-dependent manner, resulting in high levels of GILT in mature osteoclasts, which could be further augmented by γ-interferon. GILT colocalize

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Li, H., та H. Chen. "11β-HYDROXYSTEROID DEHYDROGENASE TYPE 1 KNOCK-OFF PROTECTS AGAINST OVARIECTOMY-INDUCED OSTEOPOROSIS BY INHIBITING OSTEOCLAST ACTIVATION". Orthopaedic Proceedings 105-B, SUPP_8 (2023): 15. http://dx.doi.org/10.1302/1358-992x.2023.8.015.

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Osteoporosis is a common problem in postmenopausal women and the elderly. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a bi-directional enzyme that primarily activates glucocorticoids (GCs) in vivo, which is a considerable potential target as treatment for osteoporosis. Previous studies have demonstrated its effect on osteogenesis, and our study aimed to demonstrate its effect on osteoclast activation.In vivo, we used 11β-HSD1 knock-off (KO) and C57BL6/J mice to undergo the ovariectomy-induced osteoporosis (OVX). In vitro, In vivo, We used 11β-HSD1 knockoff (KO) and C57BL6/J mice to u

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Dai, Jingjin, Rui Dong, Xinyun Han, et al. "Osteoclast-derived exosomal let-7a-5p targets Smad2 to promote the hypertrophic differentiation of chondrocytes." American Journal of Physiology-Cell Physiology 319, no. 1 (2020): C21—C33. http://dx.doi.org/10.1152/ajpcell.00039.2020.

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The invasion of osteoclasts into the cartilage via blood vessels advances the process of endochondral ossification, and dysregulation of dynamic intercellular interactions results in skeletal dysplasias. Although the regulation of osteoclasts by growth plate chondrocytes has been reported in detail, the effect of osteoclasts on chondrocytes remains to be determined. In this study, ATDC5 cells and bone marrow mesenchymal stem cells were differentiated into chondrocytes and treated with conditioned medium obtained from bone marrow macrophages differentiated to osteoclast precursors and osteoclas

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Yagi, Mitsuru, Takeshi Miyamoto, Yumi Sawatani, et al. "DC-STAMP is essential for cell–cell fusion in osteoclasts and foreign body giant cells." Journal of Experimental Medicine 202, no. 3 (2005): 345–51. http://dx.doi.org/10.1084/jem.20050645.

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Osteoclasts are bone-resorbing cells that play a pivotal role in bone remodeling. Osteoclasts form large multinuclear giant cells by fusion of mononuclear osteoclasts. How cell fusion is mediated, however, is unclear. We identify the dendritic cell–specific transmembrane protein (DC-STAMP), a putative seven-transmembrane protein, by a DNA subtraction screen between multinuclear osteoclasts and mononuclear macrophages. DC-STAMP is highly expressed in osteoclasts but not in macrophages. DC-STAMP–deficient mice were generated, and osteoclast cell fusion was completely abrogated in homozygotes des

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Kukita, T., A. Kukita, T. Watanabe, and T. Iijima. "Osteoclast differentiation antigen, distinct from receptor activator of nuclear factor kappa B, is involved in osteoclastogenesis under calcitonin-regulated conditions." Journal of Endocrinology 170, no. 1 (2001): 175–83. http://dx.doi.org/10.1677/joe.0.1700175.

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Although calcitonin has been clinically utilized as a primary treatment for several metabolic bone diseases, its inhibitory effects against osteoclastic function diminish after several days owing to the calcitonin 'escape phenomenon'. We have previously found a unique cell-surface antigen (Kat1-antigen) expressed on rat osteoclasts. Here we show evidence that, in the presence of calcitonin, the Kat1-antigen is involved in osteoclastogenesis. Treatment of bone marrow cultures for forming osteoclast-like cells with anti-Kat1-antigen monoclonal antibody (mAb Kat1) provoked a marked stimulation of

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Gwaltney, S. M., R. J. S. Galvin, K. B. Register, R. B. Rimler, and M. R. Ackermann. "Effects of Pasteurella multocida Toxin on Porcine Bone Marrow Cell Differentiation into Osteoclasts and Osteoblasts." Veterinary Pathology 34, no. 5 (1997): 421–30. http://dx.doi.org/10.1177/030098589703400506.

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The effect of Pasteurella multocida toxin (PMT) on porcine osteoclast and osteoblast differentiation was studied using in vitro cell culture systems. When grown in the presence of Vitamin D3, isolated porcine bone marrow cells formed multinucleated cells with features characteristic of osteoclasts. Exposure of bone marrow cells to Vitamin D3 and PMT during growth resulted in formation of increased numbers and earlier appearance of osteoclasts compared to controls. Ultrafiltered medium from PMT-treated cells likewise increased osteoclast numbers, suggesting that a soluble mediator may be involv

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Huang, WH, AT Lau, LL Daniels, et al. "Detection of estrogen receptor alpha, carbonic anhydrase II and tartrate-resistant acid phosphatase mRNAs in putative mononuclear osteoclast precursor cells of neonatal rats by fluorescence in situ hybridization." Journal of Molecular Endocrinology 20, no. 2 (1998): 211–19. http://dx.doi.org/10.1677/jme.0.0200211.

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Increasing evidence suggests that estrogen deficiency in women promotes the expansion of populations of bone marrow cells that differentiate into osteoclasts under the influence of osteotropic hormones and local factors. A progressive cytoplasmic accumulation of osteoclastic bone resorbing enzymes, such as tartrate-resistant acid phosphatase (TRACP) and carbonic anhydrase II (CA II), characterizes osteoclast differentiation. To evaluate the possibility that estrogen may have a direct effect on osteoclast precursor cells, we investigated the mRNA levels of estrogen receptor a (ERa), TRACP and C

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Koyanagi, Yu, Eiko Sakai, Yu Yamaguchi, et al. "Dennd2c Negatively Controls Multinucleation and Differentiation in Osteoclasts by Regulating Actin Polymerization and Protrusion Formation." International Journal of Molecular Sciences 25, no. 21 (2024): 11479. http://dx.doi.org/10.3390/ijms252111479.

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Osteoclasts are bone-resorbing multinucleated giant cells formed by the fusion of monocyte/macrophage lineages. Various small GTPases are involved in the multinucleation and differentiation of osteoclasts. However, the roles of small GTPases regulatory molecules in osteoclast differentiation remain unclear. In the present study, we examined the role of Dennd2c, a putative guanine nucleotide exchange factor for Rab GTPases, in osteoclast differentiation. Knockdown of Dennd2c promoted osteoclast differentiation, resorption, and expression of osteoclast markers. Morphologically, Dennd2c knockdown

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Brooks, Kalia, C. Ireland, Beeton, and Rushton. "Direct Inhibition of Osteoclast Formation and Activity by the Vitamin E Isomer gamma-Tocotrienol." International Journal for Vitamin and Nutrition Research 81, no. 6 (2011): 358–67. http://dx.doi.org/10.1024/0300-9831/a000087.

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Vitamin E homologues, specifically tocotrienols, have been shown to have favorable effects on bone. They possess properties that are indicative of anti-resorptive activity, suggesting the potential for vitamin E in preventing bone loss. To investigate the anti-resorptive activity of the various vitamin E homologues, we cultured human osteoclasts from blood-derived CD14+ cells on collagen, dentin, and calcium phosphate substrates, with some samples supplemented with vitamin E homologues in their cell culture medium. These were compared to the clinically used bisphosphonate, pamidronate. Compoun

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Hayashi, Shin-Ichi, Toshiyuki Yamane, Akitomo Miyamoto, et al. "Commitment and differentiation of stem cells to the osteoclast lineage." Biochemistry and Cell Biology 76, no. 6 (1998): 911–22. http://dx.doi.org/10.1139/o98-099.

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Osteoclasts are hematopoietic cells which play important roles in bone remodeling and resorption. They have phenotypic characteristics of the monocyte/macrophage lineages. In this review we first describe the phylogeny of osteoclasts. Osteoclast generation is closely linked to the presence of bone tissues. The formation of bone cavities in aquatic animals is underdeveloped, even though they have cells which have the potential to differentiate into osteoclasts. Next we describe recent advances in our understanding of osteoclastogenesis that have resulted from the identification of critical mole

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Abdel Razik, Heba E., Miho Nakamura, Leire Bergara-Muguruza, et al. "Osteoblast-Mediated Resorption of Porous Bioactive SCPC Granules Enhances Bone Regeneration in Human Extraction Sockets." Solid State Phenomena 340 (December 23, 2022): 107–12. http://dx.doi.org/10.4028/p-32eola.

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Bone graft materials are widely used in orthopedic and maxillofacial surgeries. The controlled resorbability of the graft material is essential for bone regeneration. Hydroxyapatite and biphasic calcium phosphate bone grafts have poor resorption and limited bone conductive effects. Histology analyses of bone biopsy from SCPC grafted human extraction sockets showed complete bone regeneration and graft resorption in absence of osteoclasts and macrophages. The hypothesis of the present study is that bioactive SCPC inhibits osteoclast’s activity due to the presence of resorbable silica phase in th

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Cackowski, Frank C., Judith L. Anderson, Kenneth D. Patrene, et al. "Osteoclasts are important for bone angiogenesis." Blood 115, no. 1 (2010): 140–49. http://dx.doi.org/10.1182/blood-2009-08-237628.

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Abstract Increased osteoclastogenesis and angiogenesis occur in physiologic and pathologic conditions. However, it is unclear if or how these processes are linked. To test the hypothesis that osteoclasts stimulate angiogenesis, we modulated osteoclast formation in fetal mouse metatarsal explants or in adult mice and determined the effect on angiogenesis. Suppression of osteoclast formation with osteoprotegerin dose-dependently inhibited angiogenesis and osteoclastogenesis in metatarsal explants. Conversely, treatment with parathyroid hormone related protein (PTHrP) increased explant angiogenes

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Hulley, Philippa A., and Helen J. Knowles. "A New Method to Sort Differentiating Osteoclasts into Defined Homogeneous Subgroups." Cells 11, no. 24 (2022): 3973. http://dx.doi.org/10.3390/cells11243973.

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Osteoclasts regulate skeletal development but also drive pathological osteolysis, making them prime therapeutic targets. Osteoclast research is limited by the heterogeneity of osteoclast populations generated in vitro, where the mixture of undifferentiated monocytes, binuclear pre-osteoclasts and multinucleated osteoclasts has by necessity been considered a single osteoclast population. This study describes the differentiation of primary human CD14+ monocyte-derived osteoclasts in 3D collagen gels. These osteoclasts remained small (>95% with ≤5 nuclei) but were viable and active; when relea

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Stephens, Sébastien, and Simon Platt. "Charcot Foot and the Osteoclast: More Than Just Cytokines." Foot & Ankle Orthopaedics 4, no. 4 (2019): 2473011419S0041. http://dx.doi.org/10.1177/2473011419s00412.

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Category: Basic Sciences/Biologics Introduction/Purpose: Charcot foot is a serious complication of diabetes present in up to 13% carrying with high morbidity (dislocations, fractures, deformities) and up to 14% mortality. In Charcot, osteoclasts are found in increased numbers and with increased activity3,4 while C-telopeptide of type I collagen (CTX) is upregulated as opposed to ALP suggesting this is indeed an osteoclast and not an osteoblast disease. Methods: The scientific literature was reviewed to identify relevant osteoclastic activators and their role in the hyper activated state. We wi

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Miyauchi, Yoshiteru, Ken Ninomiya, Hiroya Miyamoto, et al. "The Blimp1–Bcl6 axis is critical to regulate osteoclast differentiation and bone homeostasis." Journal of Experimental Medicine 207, no. 4 (2010): 751–62. http://dx.doi.org/10.1084/jem.20091957.

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Controlling osteoclastogenesis is critical to maintain physiological bone homeostasis and prevent skeletal disorders. Although signaling activating nuclear factor of activated T cells 1 (NFATc1), a transcription factor essential for osteoclastogenesis, has been intensively investigated, factors antagonistic to NFATc1 in osteoclasts have not been characterized. Here, we describe a novel pathway that maintains bone homeostasis via two transcriptional repressors, B cell lymphoma 6 (Bcl6) and B lymphocyte–induced maturation protein-1 (Blimp1). We show that Bcl6 directly targets ‘osteoclastic’ mole

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Curl, Linda, Christopher Barker, Craig Dreyer, and Wayne Sampson. "A pharmacodynamic investigation into the efficacy of osteoprotegerin during aseptic inflammation." Australasian Orthodontic Journal 28, no. 2 (2012): 219–24. http://dx.doi.org/10.2478/aoj-2012-0020.

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Abstract Background: Osteoprotegerin (OPG), as an osteoclast antagonist, limits mineralised tissue resorption under physiological conditions. Previous work investigating OPG in a rat periodontal ligament (PDL) ankylosis model found no inhibitory effect on osteoclasts when OPG was administered at a dosage of 2.5mg/kg.1,2 Aims: The object of this study was to determine whether dosages higher than 2.5 mg/kg of OPG were required to limit osteoclastic activity in an aseptic inflammatory model in rats. Materials and methods: Dry ice was applied for 15 minutes to the upper right first molar crown of

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Frisch, Benjamin, John M. Ashton, Adam Olm-shipman, Lianping Xing, Craig T. Jordan, and Laura Calvi. "Reciprocal Synergistic Interactions of Leukemic Cells with Osteoclast Progenitors in the Bone Microenvironment." Blood 112, no. 11 (2008): 322. http://dx.doi.org/10.1182/blood.v112.11.322.322.

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Abstract The bone marrow provides an essential regulatory microenvironment for adult hematopoiesis, however the relationship between the bone marrow microenvironment and malignant hematopoiesis remains poorly understood. To investigate the interactions between leukemia and the bone marrow microenvironment we utilized a mouse model of blast-crisis chronic myelogenous leukemia (BC-CML), in which primitive normal murine hematopoietic cells are modified to leukemic cells by expressing the translocation products BCR/ABL and Nup98/HoxA9. The presence of each translocation was confirmed by their co-e

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Root, Sierra H., and Héctor L. Aguila. "Novel population of human monocyte and osteoclast progenitors from pluripotent stem cells and peripheral blood." Blood Advances 5, no. 21 (2021): 4435–46. http://dx.doi.org/10.1182/bloodadvances.2021004552.

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Abstract Osteoclasts are multinuclear cells of monocytic lineage, with the ability to resorb bone. Studies in mouse have identified bone marrow clonal progenitors able to generate mature osteoclast cells (OCs) in vitro and in vivo. These osteoclast progenitors (OCPs) can also generate macrophages and dendritic cells. Interestingly, cells with equivalent potential can be detected in periphery. In humans, cells with OCP activity have been identified in bone marrow and periphery; however, their characterization has not been as extensive. We have developed reproducible methods to derive, from huma

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Chellaiah, M. A., N. Kizer, R. Biswas, et al. "Osteopontin Deficiency Produces Osteoclast Dysfunction Due to Reduced CD44 Surface Expression." Molecular Biology of the Cell 14, no. 1 (2003): 173–89. http://dx.doi.org/10.1091/mbc.e02-06-0354.

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Osteopontin (OPN) was expressed in murine wild-type osteoclasts, localized to the basolateral, clear zone, and ruffled border membranes, and deposited in the resorption pits during bone resorption. The lack of OPN secretion into the resorption bay of avian osteoclasts may be a component of their functional resorption deficiency in vitro. Osteoclasts deficient in OPN were hypomotile and exhibited decreased capacity for bone resorption in vitro. OPN stimulated CD44 expression on the osteoclast surface, and CD44 was shown to be required for osteoclast motility and bone resorption. Exogenous addit

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Leightner, Amanda C., Carina Mello Guimaraes Meyers, Michael D. Evans, Kim C. Mansky, Rajaram Gopalakrishnan, and Eric D. Jensen. "Regulation of Osteoclast Differentiation at Multiple Stages by Protein Kinase D Family Kinases." International Journal of Molecular Sciences 21, no. 3 (2020): 1056. http://dx.doi.org/10.3390/ijms21031056.

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Balanced osteoclast and osteoblast activity is necessary for skeletal health, whereas unbalanced osteoclast activity causes bone loss in many skeletal conditions. A better understanding of pathways that regulate osteoclast differentiation and activity is necessary for the development of new therapies to better manage bone resorption. The roles of Protein Kinase D (PKD) family of serine/threonine kinases in osteoclasts have not been well characterized. In this study we use immunofluorescence analysis to reveal that PKD2 and PKD3, the isoforms expressed in osteoclasts, are found in the nucleus a

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Jia, D., C. A. O’Brien, S. A. Stewart, S. C. Manolagas, and R. S. Weinstein. "Glucocorticoids Act Directly on Osteoclasts to Increase Their Life Span and Reduce Bone Density." Endocrinology 147, no. 12 (2006): 5592–99. http://dx.doi.org/10.1210/en.2006-0459.

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Glucocorticoid administration to mice results in a rapid loss of bone mineral density due to an imbalance in osteoblast and osteoclast numbers. Whereas excess glucocorticoids reduce both osteoblast and osteoclast precursors, cancellous osteoclast number surprisingly does not decrease as does osteoblast number, presumably due to the ability of glucocorticoids to promote osteoclast life span. Whether glucocorticoids act directly on osteoclasts in vivo to promote their life span and whether this contributes to the rapid loss of bone with glucocorticoid excess remains unknown. To determine the dir

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Zavrski, Ivana, Monica Hecht, Holger Krebbel, et al. "Bortezomib Inhibits Human Osteoclastogenesis." Blood 108, no. 11 (2006): 1395. http://dx.doi.org/10.1182/blood.v108.11.1395.1395.

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Abstract Enhanced osteoclastogenesis in cancer-induced bone disease may be caused by intercellular interactions between tumor cells and cells of the bone marrow microenvironment. In multiple myeloma, overexpression of RANKL in the bone marrow microenvironment may lead to the activation of TRAF-signaling and in consequence to increased NF-κB and AP-1 transcriptional activities in osteoclastic lineage cells. This results in enhanced osteoclast differentiation, activation and increased bone resorption. In this study, we have examined the effects of two NF-κB inhibitors towards their inhibitory po

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Feng, Shengmei, Lianfu Deng, Wei Chen, Jianzhong Shao, Guoliang Xu, and Yi-Ping Li. "Atp6v1c1 is an essential component of the osteoclast proton pump and in F-actin ring formation in osteoclasts." Biochemical Journal 417, no. 1 (2008): 195–203. http://dx.doi.org/10.1042/bj20081073.

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Bone resorption relies on the extracellular acidification function of V-ATPase (vacuolar-type proton-translocating ATPase) proton pump(s) present in the plasma membrane of osteoclasts. The exact configuration of the osteoclast-specific ruffled border V-ATPases remains largely unknown. In the present study, we found that the V-ATPase subunit Atp6v1c1 (C1) is highly expressed in osteoclasts, whereas subunits Atp6v1c2a (C2a) and Atp6v1c2b (C2b) are not. The expression level of C1 is highly induced by RANKL [receptor activator for NF-κB (nuclear factor κB) ligand] during osteoclast differentiation

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Pavlos, Nathan J., Jiake Xu, Dietmar Riedel, et al. "Rab3D Regulates a Novel Vesicular Trafficking Pathway That Is Required for Osteoclastic Bone Resorption." Molecular and Cellular Biology 25, no. 12 (2005): 5253–69. http://dx.doi.org/10.1128/mcb.25.12.5253-5269.2005.

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ABSTRACT Rab3 proteins are a subfamily of GTPases, known to mediate membrane transport in eukaryotic cells and play a role in exocytosis. Our data indicate that Rab3D is the major Rab3 species expressed in osteoclasts. To investigate the role of Rab3D in osteoclast physiology we examined the skeletal architecture of Rab3D-deficient mice and found an osteosclerotic phenotype. Although basal osteoclast number in null animals is normal the total eroded surface is significantly reduced, suggesting that the resorptive defect is due to attenuated osteoclast activity. Consistent with this hypothesis,

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Lentzsch, Suzanne, Gulsum Anderson, Noriyoshi Kurihara, et al. "Thalidomide Derivative CC-4047 Inhibits Osteoclast Formation by down Regulation of PU.1." Blood 106, no. 11 (2005): 629. http://dx.doi.org/10.1182/blood.v106.11.629.629.

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Abstract CC-4047 (Actimid) is an immunomodulatory analog of thalidomide that has stronger anti-myeloma and anti-angiogenic activity than thalidomide, but its effects on human osteoclast lineage are unknown. Early osteoclast progenitors are of hematopoietic origin and progressively differentiate into mature bone resorbing multinucleated osteoclasts. We investigated the effects of CC-4047 and thalidomide on human osteoclastogenesis, using in vitro receptor activator of NFκ-B ligand/M-CSF stimulated culture system of bone marrow cells. Three weeks of treatment of primary bone marrow cultures with

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Andersson, G. N., and S. C. Marks. "Tartrate-resistant acid ATPase as a cytochemical marker for osteoclasts." Journal of Histochemistry & Cytochemistry 37, no. 1 (1989): 115–17. http://dx.doi.org/10.1177/37.1.2461980.

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We present a modified histochemical method for staining osteoclasts and adjacent mononuclear cells which takes advantage of the recently described substrate specificity for ATP of osteoclastic acid phosphatase. Staining of osteoclasts using ATP as substrate exhibits by light microscopy the same tartrate resistance as conventional acidic phosphatases, without the bone surface staining seen with other substrates. This feature, coupled with specific staining of fewer vicinal mononuclear cells, makes this method potentially useful for studying osteoclast ontogeny and function.

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Anderson, Gülsüm, Margarete Gries, Noriyoshi Kurihara, et al. "Thalidomide derivative CC-4047 inhibits osteoclast formation by down-regulation of PU.1." Blood 107, no. 8 (2006): 3098–105. http://dx.doi.org/10.1182/blood-2005-08-3450.

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Abstract CC-4047, an immunomodulatory analog of thalidomide, inhibits multiple myeloma with unknown effects on the human osteoclast lineage. Early osteoclast progenitors are of hematopoietic origin and differentiate into mature bone resorbing multinucleated osteoclasts. We investigated the effects of CC-4047 and thalidomide on human osteoclastogenesis, using in vitro receptor activator of NFκ-B ligand/macrophage colony-stimulating factor–stimulated bone marrow cell cultures. Treating bone marrow cultures with CC-4047 for 3 weeks decreased osteoclast formation accompanied by complete inhibition

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Robinson, Lisa J., Salvatore Mancarella, Irina L. Tourkova, John B. Barnett, Harry C. Blair, and Jonathan Soboloff. "Critical Role for the Calcium-Release Activated Calcium Channel Orai1 In RANKL-Stimulated Osteoclast Formation From Monocytic Cells." Blood 116, no. 21 (2010): 928. http://dx.doi.org/10.1182/blood.v116.21.928.928.

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Abstract Abstract 928 Calcium signals are major regulators of human osteoclast formation and function, and the molecular mechanisms underlying calcium effects are of interest as possible targets for pharmacologic regulation of bone resorption. IP3-receptor regulated release of calcium stores is linked to NFATc1 activation, which stimulates expression of key osteoclast genes in precursors, but the roles of other calcium channels in osteoclastogenesis are not clear. In particular, the identity of the channel(s) mediating extracellular calcium influx triggered by release of calcium stores remains

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Heinemann, Christiane, Josephine Adam, Benjamin Kruppke, Vera Hintze, Hans-Peter Wiesmann, and Thomas Hanke. "How to Get Them off?—Assessment of Innovative Techniques for Generation and Detachment of Mature Osteoclasts for Biomaterial Resorption Studies." International Journal of Molecular Sciences 22, no. 3 (2021): 1329. http://dx.doi.org/10.3390/ijms22031329.

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The fusion process of mononuclear monocytes into multinuclear osteoclasts in vitro is an essential process for the study of osteoclastic resorption of biomaterials. Thereby biomaterials offer many influencing factors such as sample shape, material composition, and surface topography, which can have a decisive influence on the fusion and thus the entire investigation. For the specific investigation of resorption, it can therefore be advantageous to skip the fusion on samples and use mature, predifferentiated osteoclasts directly. However, most conventional detachment methods (cell scraper, accu

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Yang, Jihyun, Jiseon Kim, Young Hee Ryu, Cheol-Heui Yun, and Seung Hyun Han. "Lipoteichoic acid from Staphylococcus aureus attenuates differentiation of pre-osteoclast into mature osteoclast (136.26)." Journal of Immunology 184, no. 1_Supplement (2010): 136.26. http://dx.doi.org/10.4049/jimmunol.184.supp.136.26.

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Abstract Bacterial virulence factors regulate differentiation and functions of osteoclasts, which mediate the bone-resorptive process. Here, we investigated the effect of a major cell wall virulence factor of Gram-positive bacteria, lipoteichoic acid (LTA), on the osteoclast differentiation. Highly-pure and structurally-intact LTA was prepared from Staphylococcus aureus through sequential application of organic solvent extraction and hydrophobic-interaction column chromatography followed by ion-exchange column chromatography. Osteoclast precursors were prepared from C57BL/6 mouse bone marrow c

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Han, Sang-Yong, June-Hyun Kim, Eun-Heui Jo, and Yun-Kyung Kim. "Eleutherococcus sessiliflorus Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-Induced Osteoclast Differentiation and Prevents Ovariectomy (OVX)-Induced Bone Loss." Molecules 26, no. 7 (2021): 1886. http://dx.doi.org/10.3390/molecules26071886.

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The aim of this study was to evaluate the effects of root bark of Eleutherococcus sessiliflorus (ES) on osteoclast differentiation and function in vitro and in vivo. In vitro, we found that ES significantly inhibited the RANKL-induced formation of TRAP-positive multinucleated osteoclasts and osteoclastic bone resorption without cytotoxic effects. ES markedly downregulated the expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1); c-Fos; and osteoclast-related marker genes, such as TRAP, osteoclast-associated receptor (OSCAR), matrix metalloproteinase-9 (MMP-9), calcitonin re

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Ariyoshi, Wataru, Shiika Hara, Ayaka Koga, Yoshie Nagai-Yoshioka та Ryota Yamasaki. "Biological Effects of β-Glucans on Osteoclastogenesis". Molecules 26, № 7 (2021): 1982. http://dx.doi.org/10.3390/molecules26071982.

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Although the anti-tumor and anti-infective properties of β-glucans have been well-discussed, their role in bone metabolism has not been reviewed so far. This review discusses the biological effects of β-glucans on bone metabolisms, especially on bone-resorbing osteoclasts, which are differentiated from hematopoietic precursors. Multiple immunoreceptors that can recognize β-glucans were reported to be expressed in osteoclast precursors. Coordinated co-stimulatory signals mediated by these immunoreceptors are important for the regulation of osteoclastogenesis and bone remodeling. Curdlan from th

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