Biointerface science: Molecular basis of articular cartilage boundary lubrication

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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.