Biointerface science: Molecular basis of articular cartilage boundary lubrication

生物界面科学：关节软骨边界润滑的分子基础

• 批准号: 355591-2009
• 负责人: Schmidt, Tannin
• 金额: $ 2.19万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=527827
• 关键词: Biointerface; science; Molecular; basis; articular

Articular cartilage is the tissue at the ends of long bones that bears load and slides relative to an apposing tissue surface in a fluid filled cavity. Such tissue-tissue interfaces in the body are called biointerfaces. The nearly frictionless articulation of cartilage in knee joints is due to the remarkable lubrication properties of cartilage and the surrounding synovial fluid. Boundary lubrication is an essential mechanism of articular cartilage lubrication where surface-to-surface contact of apposing cartilage surfaces occurs, and surface bound molecules enhance lubrication. This mode of lubrication is particularly important for the protection and maintenance of articular cartilage, and is thought to be due to interactions of molecules in synovial fluid with the articular surface. Proteoglycan 4 (PRG4), classically referred to as 'lubricin', and hyaluronan are two such molecules in synovial fluid that are also present at the surface of articular cartilage. PRG4 and hyaluronan, both alone and in combination, provide boundary lubrication of articular cartilage. The physical properties of molecules like PRG4 are generally determined by their ability to form aggregate structures called multimers. Indeed, PRG4 has recently been shown to exist in normal synovial fluid as multimers. The goal is this work is therefore to determine if the aggregation of PRG4 that occurs in normal synovial fluid affects its ability to interact with hyaluronan, to adhere to the surface of articular cartilage, and thereby function as an effective boundary lubricant. The planned experiments will use a unique combination of novel biochemical and biomechanical methods to first purify PRG4 molecules from synovial fluid, then assess their ability to interact with hyaluronan and the articular surface, and finally to provide boundary lubricating function. This work will result in significant advances in basic science by contributing to the understanding of a fundamental cartilage lubrication mechanism relevant to knee joint integrity (and potentially other biointerfaces), and orthopeadic bioengineering by providing the basis for potential development of new synovial fluid therapeutics in Canada for the treatment of injured joints or maintenance of healthy joints.

关节软骨是长骨头末端的组织，其载荷相对于液体充满的腔中的腹表面滑动。人体中的组织组织界面称为生物界面。膝关节中软骨几乎无摩擦的表达是由于软骨和周围滑液的显着润滑性能。边界润滑是关节软骨润滑的基本机制，在该机构中，发生围成软骨表面的表面向表面接触发生，并且表面结合分子增强了润滑。这种润滑模式对于保护和维持关节软骨尤为重要，被认为是由于滑液中分子与关节表面的相互作用所致。蛋白聚糖4（PRG4），通常称为“润滑剂”，而透明质酸是滑动流体中的两个这样的分子，它们也存在于关节软骨表面。 PRG4和透明质酸单独和组合都提供关节软骨的边界润滑。像PRG4这样的分子的物理特性通常取决于它们形成称为多聚体的聚集结构的能力。实际上，最近已显示PRG4在正常滑液中作为多聚体存在。因此，这项工作是为了确定正常滑液中发生的PRG4的聚集是否会影响其与透明质酸相互作用，粘附到关节软骨表面，从而将其作为有效的边界润滑剂的能力。计划的实验将使用新型生化和生物力学方法的独特组合来首先从滑液中纯化PRG4分子，然后评估它们与透明质酸和意思表面相互作用的能力，最后提供边界润滑功能。这项工作将通过理解与膝盖关节完整性相关的基本软骨润滑机制（以及潜在的其他生物界面），并通过为加拿大新型液体疗法的潜​​在开发提供基础，从而为加拿大新型关节受伤关节的新型关节或健康关节的治疗提供了潜在的基础，从而为基础科学的重大进步而取得了重大进步。