Biointerface science: Molecular basis of articular cartilage boundary lubrication

关节软骨是长骨末端的组织，在充满液体的腔中相对于相对的组织表面承受载荷和滑动。体内的这种组织-组织界面被称为生物界面。膝关节软骨的近乎无摩擦的关节是由于软骨和周围的滑液具有显著的润滑性能。边界润滑是关节软骨润滑的一种基本机制，软骨表面相互接触，表面结合的分子增强了润滑作用。这种润滑方式对关节软骨的保护和维护尤为重要，被认为是由于滑液中的分子与关节表面的相互作用所致。蛋白多糖4(PRG4)和透明质酸是滑液中的两个这样的分子，也存在于关节软骨的表面。PRG4和透明质酸单独或联合使用可为关节软骨提供边界润滑剂。像PRG4这样的分子的物理性质通常由它们形成聚集体结构(称为多聚体)的能力决定。事实上，PRG4最近被证明以多聚体的形式存在于正常的滑液中。因此，这项工作的目的是确定发生在正常滑液中的PRG4聚集是否会影响其与透明质酸相互作用的能力，从而黏附于关节软骨表面，从而发挥有效的边界润滑剂的作用。计划中的实验将使用新的生化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，并通过为加拿大潜在的用于治疗受损关节或维持健康关节的新型滑液疗法的开发提供基础，从而推动基础科学的重大进步。

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.