Mechanisms of Articular Cartilage Lubrication

描述(申请人提供)：关节软骨是身体中的许多组织之一，它相对于相对的组织表面承受载荷和滑动，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，关节表面会变得粗糙和侵蚀。这种劣化可能是由几个因素造成的，导致负荷过大、润滑机构故障或两者兼而有之。其广泛的、长期的目标是有助于理解相互作用的关节间隙的机械生物学系统，以便深入了解关节软骨润滑的机制和后果。这一建议旨在促进对润滑机制的理解，特别是滑液对关节软骨进行边界模式润滑的分子基础。有待检验的总体假设是，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而发生的，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。这一假说表明，某些分子在关节腔内的浓度和它们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是：假设1：通过边界润滑降低软骨-软骨界面摩擦力的SF成分是Lub/SZP、SAPL和HA，它们单独或联合作用。假设2：通过边界润滑降低软骨-软骨界面磨损量的SF成分是Lub/SZP、SAPL和HA，它们单独作用或联合作用。假设3：根据Lub/SZP、SAPL和HA的水平以及针对假设1和2的研究结果，生物合成和实际SF的溶液为关节软骨提供摩擦和磨损性能。为了解决每个假设，建议从软骨-软骨测试配置中对切除的骨软骨碎片进行组织水平的研究开始。他们继续对关节软骨进行选定的关节规模的生物力学实验。与公共卫生的相关性：上述假设的确认与关节健康的正常维持和关节炎疾病的致病过程都相关。这些信息最终可能有助于对滑液隔室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.