Добірка наукової літератури з теми "Hindlimb immobilisation"

Contractile proteins exist as a number of isoforms that show a developmental and tissue-specific pattern of expression. Using gene-specific cDNA probes, the expression of the sarcomeric myosin heavy chain (MHC) multi-gene family and of cardiac (foetal) alpha-actin was analysed in three different rat hindlimb muscles immobilised for 5 days in either the shortened or lengthened positions. For each of the MHC genes normally expressed in adult muscle (slow, IIA and IIB), the effect of disuse alone (immobilisation in the shortened position) upon expression was markedly different to that of passive stretch (immobilisation in the lengthened position) in each of the three muscles. However, the same adult sarcomeric myosin heavy chain gene can be affected in a different, or even opposite, manner by either disuse or passive stretch depending on the muscle in which it is being expressed. The fast IIB MHC gene, for example, exhibits a rapid induction in the slow postural soleus muscle, in response to disuse but no such induction occurs in the faster plantaris and gastrocnemius muscles. Furthermore, the induction of this gene in the soleus was prevented by passive stretch. The MHC gene, normally only expressed in embryonic skeletal muscle, showed a similar response in all three muscles and was reinduced in adult muscle in response to passive stretch but not by disuse alone. In contrast, the isoform of alpha-actin which is normally only present in significant quantities in embryonic skeletal muscle and which is reduced postnatally, is not reinduced by passive stretch but is reduced still further by immobilisation in the shortened position.

ABSTRACT Fetal activity in utero is a normal part of pregnancy and reduced or absent movement can lead to long-term skeletal defects, such as Fetal Akinesia Deformation Sequence, joint dysplasia and arthrogryposis. A variety of animal models with decreased or absent embryonic movements show a consistent set of developmental defects, providing insight into the aetiology of congenital skeletal abnormalities. At developing joints, defects include reduced joint interzones with frequent fusion of cartilaginous skeletal rudiments across the joint. At the spine, defects include shortening and a spectrum of curvature deformations. An important question, with relevance to possible therapeutic interventions for human conditions, is the capacity for recovery with resumption of movement following short-term immobilisation. Here, we use the well-established chick model to compare the effects of sustained immobilisation from embryonic day (E)4-10 to two different recovery scenarios: (1) natural recovery from E6 until E10 and (2) the addition of hyperactive movement stimulation during the recovery period. We demonstrate partial recovery of movement and partial recovery of joint development under both recovery conditions, but no improvement in spine defects. The joints examined (elbow, hip and knee) showed better recovery in hindlimb than forelimb, with hyperactive mobility leading to greater recovery in the knee and hip. The hip joint showed the best recovery with improved rudiment separation, tissue organisation and commencement of cavitation. This work demonstrates that movement post paralysis can partially recover specific aspects of joint development, which could inform therapeutic approaches to ameliorate the effects of human fetal immobility. This article has an associated First Person interview with the first author of the paper.

The regulation of glucose uptake and mass in skeletal muscle are essential for the maintenance of functional capacity, general health, and quality of life. Skeletal muscle can be categorised into two major types, glycolytic and oxidative muscles. The regulation of muscle glucose uptake varies between the two muscle types, dependent on specific conditions, such as whether or not insulin is present, and whether the muscle is at rest or following exercise. Furthermore, muscle atrophy in response to disuse, disease or aging also occurs in a muscle type-specific manner. However, the exact mechanisms underlying these muscle type specificities still remain unclear. Emerging evidence indicates that undercarboxylated osteocalcin (ucOC), a hormone secreted from bone, may play a role in the regulation of muscle glucose uptake and muscle mass. The signalling pathways underlying the ucOC effect on muscle are not clear, but may include G protein-coupled receptor, class C, group 6, member A (GPRC6A) as the receptor, along with the activation of protein kinase B (Akt), extracellular signal-regulated kinases (ERK), 5' adenosine monophosphate-activated protein kinase (AMPK), protein kinase C (PKC), Akt substrate of 160kD (AS160), mammalian target of rapamycin complex 1 (mTORC1), and/or the class O of forkhead box transcription factors (FOXOs). It is also not clear whether the effect of ucOC on muscle glucose uptake and the loss of ucOC signalling during muscle atrophy are muscle type-specific, contributing to the muscle type specificities in glucose uptake regulation and muscle wasting, respectively. Therefore, this PhD thesis aimed to explore the link between ucOC and muscle glucose uptake (under various conditions) and muscle mass in glycolytic and oxidative muscles, as well as investigate the underlying mechanisms. The thesis contains four separate but related studies, all of which have been published in top journals in the area of bone and mineral research.