Mechanisms of Articular Cartilage Lubrication

描述（由申请人提供）：关节软骨是人体中承受载荷和相对于相邻组织表面滑动的众多组织之一，具有显著的摩擦学特性——低摩擦、低磨损和多种润滑模式，以降低摩擦和/或磨损。然而，在衰老和骨关节炎中，关节表面变得粗糙和侵蚀。这种劣化可能是多种因素导致的结果，包括过载、润滑机制失效或两者兼而有之。广泛的，长期的目标是有助于理解相互作用的关节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。本研究旨在促进对润滑机制的理解，特别是滑膜液对关节软骨边界模式润滑的分子基础。要测试的总体假设是，关节软骨的边界润滑是通过滑液分子与关节表面的相互作用发生的，减少了边界模式的摩擦和磨损，从而有助于健康关节的机械维护。这一假设表明，关节腔内某些分子的浓度及其在关节表面的粘附性是功能性润滑的关键决定因素。需要检验的具体假设有：假设1：通过边界润滑降低软骨-软骨界面摩擦的SF成分是Lub/SZP、SAPL和HA，它们单独或联合起作用。假设2：通过边界润滑降低软骨-软骨界面磨损的SF成分是Lub/SZP、SAPL和HA，它们单独或联合起作用。假设3：生物合成和实际SF溶液根据Lub/SZP、SAPL和HA水平提供关节软骨的摩擦和磨损性能，以及针对假设1和2的研究结果。为了解决每个假设，研究建议从软骨对软骨试验配置中切除的骨软骨碎片的组织水平研究开始。他们继续选择关节软骨的关节尺度生物力学实验。与公共卫生的相关性：上述假设的证实与关节健康的正常维持和关节炎疾病的致病过程都有关。这些信息可能最终有助于对滑液腔中具有机械重要性的分子进行诊断分析和治疗操作。

DESCRIPTION (provided by applicant): 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 healthy joints. 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.