MECHANICAL SIGNAL TRANSDUCTION MECHANISMS IN CARTILAGE

关节软骨作为一种承重组织， 机械环境的影响。 虽然机械的影响 关节软骨上的力被很好地描述， 造成这些影响的机制尚不清楚。的目标 这些研究旨在阐明细胞内信号转导途径 介导软骨负荷的生物学效应。 这些 研究将集中在以下四个相关的具体目标上。 1. 测试静态和动态压缩载荷的假设 影响关节软骨细胞不同的信号传导途径 软骨细胞 2. 检验整合素启动和 生长因子受体启动的途径有助于 关节软骨细胞的压缩负荷。 3.识别特定 受机械调节的信号转导元件 压缩关节软骨细胞。4. 测试假设，一些 老年软骨具有信号转导缺陷， 表现在其对机械压缩的响应上。 这些研究将使用牛和人的关节软骨进行 外植体和凝胶悬浮培养系统，侧重于近端 （膜和细胞质）事件介导细胞对 细胞外信号 这些研究表明，机械因素激活 特异性信号转导途径不仅可以帮助我们了解 控制正常关节软骨的分子机制 稳态，但将作为研究途径的基础， 破坏可能导致软骨疾病。

Articular cartilage functions as a load-bearing tissue that is regulated by its mechanical environment. Although the effects of mechanical forces on articular cartilage are well-described, the molecular mechanisms responsible for these effects are not clear. The goal of these studies is to elucidate intracellular signal transduction pathways that mediate the biological effects of loading on cartilage. These studies will focus on the following four related specific aims. 1. Test the hypothesis that static and dynamic compressive loads influence distinct signal transduction pathways in articular chondrocytes. 2. Test the hypothesis that integrin-initiated and growth factor receptor-initiated pathways contribute to the response of articular chondrocytes to compressive loads. 3. Identify the specific signal transduction elements that are regulated by mechanical compression in articular chondrocytes. 4. Test the hypothesis that some aged cartilage possesses a defect in signal transduction that is manifested in its response to mechanical compression. These studies will conducted using bovine and human articular cartilage explant and gel suspension culture systems, focusing on proximal (membrane and cytoplasmic) events that mediate cell responses to extracellular signals. The demonstration by these studies that mechanical factors activate specific signal transduction pathways would not only lend insight into the molecular mechanisms that govern normal articular cartilage homeostasis, but would serve as a basis for investigating pathways whose disruption may contribute to cartilage disease.