Diminished Cartilage Lubricating Ability of Human OA Synovial Fluid Deficient in PRG4: Restoration through PRG4 Supplementation

INTRODUCTION: Proteoglycan 4 (PRG4) is a mucinous glycoprotein present in synovial fluid (SF) that contributes to boundary lubrication of articular cartilage in a dose-dependent manner. PRG4 interacts with hyaluronan (HA), another dose-dependent cartilage boundary lubricant, to further decrease friction to levels near that of SF. Concentrations of PRG4 in human SF (hSF) have been reported to be decreased immediately after acute injury, returning to normal levels in 1 year, and increased in late stage osteoarthritis (OA). Concentrations of HA have been reported to remain normal in advanced OA, although molecular weight (MW) distribution has been shown to shift lower. The lubricating ability of SF void of PRG4, as well as that after injury, has been reported to be diminished. Conversely, SF lubricating ability appears to remain normal in advanced OA. Collectively these studies suggest that SF deficient in PRG4 lacks normal cartilage lubricating ability, yet it remains unclear if PRG4 levels remain normal in all chronic OA SF. The objectives of this study were to 1) quantify PRG4 and HA content in normal and chronic OA hSF samples 2) assess the human cartilage boundary lubricating ability of OA hSF deficient in PRG4, with and without supplementation of physiological levels of PRG4+/-HA, compared to normal hSF.