MECHANICAL SIGNAL TRANSDUCTION MECHANISMS IN CARTILAGE

关节软骨作为受调节的承重组织发挥作用 受其机械环境的影响。尽管机械的影响 对关节软骨的作用力是很好地描述的，分子 造成这些影响的机制尚不清楚。的目标是 这些研究是为了阐明细胞内的信号转导途径 它介导了负载对软骨的生物学效应。这些 研究将侧重于以下四个相关的具体目标。 1.检验静态和动态压缩载荷的假设 影响关节内不同的信号转导通路 软骨细胞。2.检验整合素启动和整合的假设 生长因子受体启动的通路有助于 关节软骨细胞对压缩载荷。3.确定具体的 由机械调节的信号转导元件 关节软骨细胞受压。4.检验以下假设 衰老的软骨在信号转导方面存在缺陷，即 表现为对机械压缩的反应。 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，重点放在近端 (膜和细胞质)介导细胞反应的事件 细胞外信号。 这些研究表明，机械因素会激活 特定的信号转导途径不仅能让我们洞察 控制正常关节软骨的分子机制 动态平衡，但将作为研究其途径的基础 破坏可能会导致软骨疾病。

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.