Osteocyte Modulatin of muscle function during aging

衰老性肌肉减少症是一个多方面的健康问题，由于肌肉减少症和 骨质疏松症通常是相关的或同时发生的病症。目前的解释是肌肉减少症 有助于骨质疏松症，因为肌肉，通过收缩和拉伸的负荷力， 骨骼的合成代谢刺激剂。这种观点基本上否定了从骨骼到肌肉的信号传递潜力。 尽管如此，高度创新的新研究已经发现了内分泌功能， 可能通过未知机制影响肌肉的骨骼。的主要目标 子项目2是了解从骨细胞到肌肉的通讯，以及衰老如何影响这种通讯。 通信我们的初步研究有力地支持了我们的观点，即骨骼通过 调节肌肉成肌分化。细胞内钙稳态和收缩功能。 此外，我们的数据现在表明，这种骨骼肌肉信号传导是由Wnt/β-连环蛋白介导的。 最重要的是，这种信号在衰老过程中会受到损害。所以我们 假设骨细胞通过调节Wnt/β-连环蛋白途径的因子向肌肉传递信号， 对于肌细胞分化、Ca 2-*-稳态和收缩功能很重要。在老化过程中， 从骨细胞到肌肉的信号传导受到损害，从而导致与衰老相关的 肌肉功能我们将通过以下具体目标来检验这一假设：具体目标1： 骨细胞调节肌源性分化的分子机制，以及Ca 2-i- 作为年龄的函数的稳态。具体目标2：确定骨细胞因子如何调节肌肉 收缩力作为年龄的函数。这些研究首次提出系统地研究 通过研究Wnt/β-连环蛋白信号通路对肌肉功能老化衰退的贡献， 在细胞和分子水平上的骨骼-肌肉串扰。这样的知识将有助于 确定用于开发肌肉减少症治疗干预措施的新靶点， 骨质疏松

Aging sarcopenia is a multifaceted health problem that is further complicated since sarcopenia and osteoporosis are normally related or simultaneous conditions. The current interpretation is that sarcopenia contributes to osteoporosis because muscles, through the loading forces of contraction and stretch, are anabolic stimulators of bones. This view essentially negates the potential for signaling from bone to muscle. Nevertheless, highly innovative, emerging new research has led to the discovery of endocrine functions of bone that could potentially influence muscle through yet unknown mechanisms. The major goal of Subproject 2 is to understand the communication from the osteocyte to muscle, and how aging affects such communication. Our preliminary studies strongly support our concept that bone signals to muscle by modulating muscle myogenic differentiation. Intracellular calcium homeostasis and contractile function. Furthermore, our data now suggests that this bone-muscle signaling Is mediated by the Wnt/b-catenin pathway, and of utmost importance, that this signaling Is compromised during aging. Therefore, we hypothesize that osteocytes signal to muscles via factors that modulate the Wnt/b-catenin pathway and are important for myogenic differentiation, Ca2-*- homeostasis, and contractile function. During aging the signaling from osteocytes to muscles is compromised, thereby contributing to the aging-related decline in muscle function. We will test this hypothesis by tiie following specific aims: Specific Aim 1: To determine the molecular mechanisms by which osteocytes modulate muscle myogenic differentiation, and Ca2-i- homeostasis as a function of age. Specific Aim 2: To determine how osteocyte factors modulate muscle contractility as a function of age. These studies are the first to propose to systematically investigate the contribution of the Wnt/beta-catenin signaling pathway to the aging decline in muscle function by studying the bone-muscle crosstalk at the cellular and molecular levels. Such knowledge will assist with the identification of new targets for development of therapeutic interventions for sarcopenia and osteoporosis.