Mechanisms of Articular Cartilage Lubrication

关节软骨润滑的机制

• 批准号: 7147152
• 负责人: Robert L Sah
• 金额: $ 33.98万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-10 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7147152
• 关键词: animal tissue; articular cartilage; biomechanics; biosynthesis; cytokine; hyaluronate; intermolecular interaction; musculoskeletal injury; osteoarthritis; phospholipids; proteoglycan; shear stress; skeletal stress; surface property; synovial fluid; synovial membrane; tissue /cell culture

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.

描述（由申请人提供）：关节软骨是体内许多组织中的一种，其承受负荷并相对于具有显著摩擦学特性的相对组织表面滑动-低摩擦、低磨损和多种润滑模式以降低摩擦和/或磨损。然而，在老化和骨关节炎中，关节面变得粗糙和侵蚀。这种劣化可能是导致过度负载、润滑机构故障或两者的几个因素的结果。广泛的，长期的目标是促进相互作用的关节腔室的机械生物学系统的理解，以深入了解关节软骨润滑的机制和后果。该建议旨在推进润滑机制的理解，特别是关节软骨滑液边界模式润滑的分子基础。待测试的总体假设是关节软骨的边界润滑通过滑液分子与关节面的相互作用发生，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，关节腔内某些分子的浓度及其在关节面的粘附是功能性润滑的关键决定因素。待检验的具体假设为：假设1：通过边界润滑降低软骨-软骨界面处摩擦的SF组分为Lub/SZP、SAPL和HA，单独或组合起作用。假设二：通过边界润滑降低软骨-软骨界面磨损的SF组分是Lub/SZP、SAPL和HA，单独或组合作用。假设三：根据Lub/SZP、SAPL和HA的水平以及解决假设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。为了解决每一个假设，研究建议开始与组织水平的研究切除骨软骨碎片在软骨对软骨的测试配置。他们继续对关节软骨进行选定的关节规模生物力学实验。与公共卫生的相关性：上述假说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。这样的信息可能最终有助于诊断分析和治疗操纵的分子的机械重要性，在滑液室。