Osteocyte Modulatin of muscle function during aging

老年性骨质疏松症是一个多方面的健康问题，由于骨质疏松症和 骨质疏松症通常是相关的或同时发生的情况。目前的解释是石棺减少症 会导致骨质疏松症，因为肌肉通过收缩和拉伸的负载力 骨骼的合成代谢刺激物。这一观点从本质上否定了从骨骼到肌肉的信号传递潜力。 然而，高度创新的、不断涌现的新研究导致了内分泌功能的发现 骨骼可以通过未知的机制潜在地影响肌肉。的主要目标是 子项目2是了解骨细胞与肌肉之间的联系，以及衰老对这种联系的影响 沟通。我们的初步研究有力地支持了我们的概念，即骨骼通过 调节肌肉的肌源性分化。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-肌肉信号转导是由Wnt/b-连接蛋白介导的 最重要的是，这种信号在衰老过程中受到损害。因此，我们 假设骨细胞通过调节Wnt/b-连环蛋白途径的因子向肌肉发出信号，并 对肌源性分化、钙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：确定 骨细胞调节肌肉成肌分化的分子机制，以及钙离子-I- 作为年龄的函数的动态平衡。特定目标2：确定骨细胞因子如何调节肌肉 作为年龄的函数的收缩能力。这些研究是第一次提出系统地研究 Wnt/β-catenin信号通路在肌肉功能衰老中的作用 骨骼-肌肉在细胞和分子水平上的串扰。这些知识将有助于 确定新的靶点用于开发治疗骨质疏松症的干预措施 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.