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Mechanisms of Articular Cartilage Lubrication

关节软骨润滑的机制

基本信息

批准号：
7903846
负责人：
Robert L Sah
金额：
$ 18.4万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-18 至 2011-09-17
项目状态：
已结题

项目摘要

Articular cartilage is one of a number of tissues in the body that bears load and slides relative to an apposing tissue surface with remarkable tribological properties¿low friction, low wear, and multiple modes of lubrication acting to lower friction and/or wear. However, in aging and osteoarthritis, the articular surface becomes roughened and eroded. Such deterioration may be the result of several factors leading to excessive loading, a failure in lubrication mechanisms, or both. The broad, long-term objectives are to contribute to the understanding of the mechanobiological system of the interacting joint compartments in order to gain insight into the mechanisms and consequences of lubrication of articular cartilage in joints. This proposal seeks to advance the understanding of lubrication mechanisms, in particular the molecular basis for boundary-mode lubrication of articular cartilage by synovial fluid. The overall hypothesis to be tested is that boundary lubrication of articular cartilage occurs via interactions of synovial fluid molecules with the articular surface, reducing boundary-mode friction and wear, and thereby contributing to the mechanical maintenance of healthyjoints. This hypothesis suggests that the concentration of certain molecules within the joint cavity and their adherence at the articular surface are critical determinants of functional lubrication. The specific hypotheses to be tested are: Hypothesis 1: The SF components that lower friction at a cartilage-cartilage interface via boundary lubrication are Lub/SZP, SAPL, and HA, acting alone or in combination. Hypothesis 2: The SF components that lower wear at a cartilage-cartilage interface via boundary lubrication are Lub/SZP, SAPL, and HA, acting alone or in combination. Hypothesis 3: Solutions of biosynthetic and actual SF provide articular cartilage with friction and wear properties according to levels of Lub/SZP, SAPL, and HA, and results of the studies addressing Hypotheses 1 and 2. To address each hypothesis, studies are proposed beginning with tissue-level studies on excised osteochondral fragments in a cartilage-on-cartilage test configuration. They proceed to selected joint-scale biomechanical experiments on articulating cartilage. Relevance to Public Health: Confirmation of the above hypotheses is relevant both to the normal maintenance of joint health and to pathogenic processes in arthritic disease. Such information may ultimately facilitate diagnostic analysis and therapeutic manipulation of molecules of mechanical importance in the synovial fluid compartment.

关节软骨是身体中承受负荷并相对于关节滑动的许多组织之一。贴附组织表面，具有显著的摩擦学性能，低摩擦，低磨损，多种模式，起到降低摩擦和/或磨损作用的润滑。然而，在衰老和骨关节炎中，变得粗糙并被侵蚀。这种恶化可能是几个因素导致的结果，负载、润滑机构故障或两者。广泛的长期目标是促进了解相互作用的关节间室的机械生物学系统，以便深入了解关节软骨润滑的机制和后果。这项建议旨在推进润滑机制的理解，特别是边界模式的分子基础滑液对关节软骨的润滑。待检验的总体假设是关节软骨的边界润滑通过相互作用发生滑液分子与关节面接触，减少边界模式摩擦和磨损，从而有助于健康关节的机械维护。这一假设表明，关节腔内的某些分子及其在关节表面的粘附是关键的决定因素功能性润滑。待检验的具体假设为：假设1：SF组件通过边界润滑降低软骨-软骨界面处的摩擦是Lub/SZP、SAPL和HA，单独或联合作用。假设2：通过边界润滑降低软骨-软骨界面磨损的SF部件是Lub/SZP、SAPL和HA，单独或联合作用。假设3：生物合成和实际SF的解决方案为关节软骨提供摩擦和磨损根据Lub/SZP、SAPL和HA水平的特性以及研究结果假设1和2。为了解决每一个假设，研究建议从组织水平的研究开始，软骨对软骨测试配置中的骨软骨碎片。他们继续选择联合规模关节软骨的生物力学实验。与公共卫生的相关性：上述假设的证实与正常维持关节健康和关节炎疾病的致病过程。这些信息最终可能有助于诊断分析和治疗操纵分子的机械重要性，滑液室。