Cartilage boundary lubricating ability of aldehyde modified proteoglycan 4 (PRG4-CHO)

Abstract

Proteoglycan 4 (PRG4), also known as lubricin1 and superficial zone protein2, is a mucinous glycoprotein that is present in synovial fluid (SF) and at the surface of articular cartilage, where it functions as a critical boundary lubricant necessary for joint health3. High friction and high wear are amongst many factors that may contribute to cartilage degeneration4. PRG4 is critical in reducing friction and minimising surface tissue shear5 at the surface of cartilage, thus preventing the degradation of cartilage through boundary lubrication. Indeed, an increased coefficient of friction in PRG4-knockout mice is associated with increased wear of the articular surface6. Furthermore, intra-articular injection of PRG4 has been shown to prevent cartilage degradation in post-injury rat models of osteoarthritis (OA)7. A recent study, motivated by diminished PRG4 levels in SF associated with early OA, demonstrated aldehyde modification of PRG4 (PRG4-CHO) significantly enhanced its binding to a depleted articular surface8. Such modification may contribute to an improved biotherapeutic treatment of early OA with PRG4 through enhanced residence time within the joint and/or binding to the articular cartilage surface. However, it remains to be determined if PRG4-CHO maintains the friction-reducing ability of unmodified PRG4. Therefore, the objective of this study was to assess the cartilage boundary lubricating ability of PRG4-CHO versus unmodified PRG4 using a previously described in-vitro cartilage-cartilage friction test5,9. The findings of this study indicate that aldehyde modification does not significantly affect the protein structure or lubricating function of PRG4, and PRG4-CHO is an effective friction reducing cartilage boundary lubricant. These results, together with previously published data8, collectively suggest PRG4-CHO may be useful in molecular resurfacing strategies for tissue surfaces requiring lubrication, and potentially other biointerfaces or biomaterials as well.