Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, MA 02131, USA.
Bone. 2010 May;46(5):1226-37. doi: 10.1016/j.bone.2010.01.382. Epub 2010 Feb 10.
There are both theoretical and empirical underpinnings that provide evidence that the musculoskeletal system develops, functions, and ages as a whole. Thus, the risk of osteoporotic fracture can be viewed as a function of loading conditions and the ability of the bone to withstand the load. Both bone loss (osteoporosis) and muscle wasting (sarcopenia) are the two sides of the same coin, an involution of the musculoskeletal system. Skeletal loads are dominated by muscle action; both bone and muscle share environmental, endocrine and paracrine influences. Muscle also has an endocrine function by producing bioactive molecules, which can contribute to homeostatic regulation of both bone and muscle. It also becomes clear that bone and muscle share genetic determinants; therefore the consideration of pleiotropy is an important aspect in the study of the genetics of osteoporosis and sarcopenia. The aim of this review is to provide an additional evidence for existence of the tight genetic co-regulation of muscles and bones, starting early in development and still evident in aging. Recently, important papers were published, including those dealing with the cellular mechanisms and anatomic substrate of bone mechanosensitivity. Further evidence has emerged suggesting that the relationship between skeletal muscle and bone parameters extends beyond the general paradigm of bone responses to mechanical loading. We provide insights into several pathways and single genes, which apparently have a biologically plausible pleiotropic effect on both bones and muscles; the list is continuing to grow. Understanding the crosstalk between muscles and bones will translate into a conceptual framework aimed at studying the pleiotropic genetic relationships in the etiology of complex musculoskeletal disease. We believe that further progress in understanding the common genetic etiology of osteoporosis and sarcopenia will provide valuable insight into important biological underpinnings for both musculoskeletal conditions. This may translate into new approaches to reduce the burden of both conditions, which are prevalent in the elderly population.
有理论和经验基础为证，表明肌肉骨骼系统作为一个整体进行发育、运作和衰老。因此，骨质疏松性骨折的风险可以看作是负荷条件和骨骼承受负荷能力的函数。骨丢失（骨质疏松症）和肌肉减少（肌肉减少症）是同一硬币的两面，是肌肉骨骼系统退化的表现。骨骼负荷主要由肌肉活动产生；骨骼和肌肉都受到环境、内分泌和旁分泌的影响。肌肉还通过产生生物活性分子发挥内分泌功能，这有助于骨骼和肌肉的内稳态调节。很明显，骨骼和肌肉共享遗传决定因素；因此，多效性的考虑是研究骨质疏松症和肌肉减少症遗传的一个重要方面。本综述的目的是提供更多证据证明肌肉和骨骼之间存在紧密的遗传共同调节，这种调节从早期发育开始，在衰老时仍然存在。最近发表了一些重要的论文，包括涉及骨骼机械敏感性的细胞机制和解剖学基础的论文。进一步的证据表明，骨骼肌肉和骨骼参数之间的关系超出了骨骼对机械负荷反应的一般范例。我们深入探讨了几个途径和单个基因，这些途径和基因显然对骨骼和肌肉具有合理的多效性影响；这个清单还在不断增加。了解肌肉和骨骼之间的串扰将转化为一个概念框架，旨在研究复杂肌肉骨骼疾病病因中的多效性遗传关系。我们相信，进一步了解骨质疏松症和肌肉减少症的共同遗传病因将为这两种肌肉骨骼疾病的重要生物学基础提供有价值的见解。这可能转化为减少这两种在老年人群中普遍存在的疾病负担的新方法。
