Biointerface science: Molecular basis of articular cartilage boundary lubrication

关节软骨是位于长骨末端的组织，它在充满液体的腔中承受载荷并相对于相邻的组织表面滑动。人体中这样的组织-组织界面被称为生物界面。膝关节软骨几乎无摩擦的关节是由于软骨和周围滑液的显著润滑特性。边界润滑是关节软骨润滑的重要机制，相邻软骨表面发生表面接触，表面结合分子增强润滑作用。这种润滑模式对关节软骨的保护和维持特别重要，并且被认为是由于滑膜液中分子与关节表面的相互作用。蛋白多糖4 (PRG4)，通常被称为“润滑素”，和透明质酸是滑膜液中的两种这样的分子，它们也存在于关节软骨表面。PRG4和透明质酸，单独或联合，提供关节软骨的边界润滑。像PRG4这样的分子的物理性质通常是由它们形成聚合结构的能力决定的，这种聚合结构被称为多聚体。事实上，PRG4最近被证明作为多聚体存在于正常的滑液中。因此，这项工作的目的是确定正常滑液中PRG4的聚集是否影响其与透明质酸相互作用的能力，从而粘附在关节软骨表面，从而发挥有效的边界润滑剂的作用。计划中的实验将采用新颖的生物化学和生物力学方法的独特组合，首先从滑液中纯化PRG4分子，然后评估它们与透明质酸和关节表面相互作用的能力，最后提供边界润滑功能。这项工作将有助于理解与膝关节完整性（以及潜在的其他生物界面）相关的基本软骨润滑机制，从而在基础科学和骨科生物工程方面取得重大进展，为加拿大治疗受伤关节或维持健康关节的新滑膜液疗法的潜在发展提供基础。

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.