Evidence for pleiotropic factors in genetics of the musculoskeletal system.
Evidence for pleiotropic factors in genetics of the musculoskeletal system.
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DOI：
10.1016/j.bone.2010.01.382
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发表时间：
2010-05
期刊：
影响因子：
4.1
通讯作者：
Kiel DP
中科院分区：
文献类型：
--
作者：
Karasik D;Kiel DP
理论和经验基础都提供了肌肉骨骼系统作为一个整体的发育、功能和年龄的证据。因此，骨质疏松性骨折的风险可以被视为负载条件和骨骼承受负载的能力的函数。骨质流失（骨质疏松症）和肌肉萎缩（肌肉减少症）是同一枚硬币的两面，即肌肉骨骼系统的退化。骨骼负荷主要由肌肉活动决定；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而具有内分泌功能，这有助于骨骼和肌肉的稳态调节。人们还清楚地知道，骨骼和肌肉具有共同的遗传决定因素。因此，多效性的考虑是骨质疏松症和肌肉减少症遗传学研究的一个重要方面。本次综述的目的是提供额外的证据，证明肌肉和骨骼存在严格的遗传共同调节，这种调节从发育早期开始，并且在衰老过程中仍然很明显。最近，发表了重要论文，包括涉及骨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式。我们提供了对几种途径和单个基因的见解，这些途径和单个基因显然对骨骼和肌肉具有生物学上合理的多效性作用；该名单还在继续增长。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学中的多效性遗传关系。我们相信，在了解骨质疏松症和肌肉减少症的常见遗传病因方面取得的进一步进展将为了解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。这可能会转化为减轻这两种疾病负担的新方法，这两种疾病在老年人口中普遍存在。
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.