Specific\nDegradation of the Mucin Domain of Lubricin\nin Synovial Fluid Impairs Cartilage Lubrication

Progressive cartilage degradation,\nsynovial inflammation,\nand joint\nlubrication dysfunction are key markers of osteoarthritis. The composition\nof synovial fluid (SF) is altered in OA, with changes to both hyaluronic\nacid and lubricin, the primary lubricating molecules in SF. Lubricin’s\ndistinct bottlebrush mucin domain has been speculated to contribute\nto its lubricating ability, but the relationship between its structure\nand mechanical function in SF is not well understood. Here, we demonstrate\nthe application of a novel mucinase (StcE) to selectively degrade\nlubricin’s mucin domain in SF to measure its impact on joint\nlubrication and friction. Notably, StcE effectively degraded the lubricating\nability of SF in a dose-dependent manner starting at nanogram concentrations\n(1–3.2 ng/mL). Further, the highest StcE doses effectively\ndegraded lubrication to levels on par with trypsin, suggesting that\ncleavage at the mucin domain of lubricin is sufficient to completely\ninhibit the lubrication mechanism of the collective protein component\nin SF. These findings demonstrate the value of mucin-specific experimental\napproaches to characterize the lubricating properties of SF and reveal\nkey trends in joint lubrication that help us better understand cartilage\nfunction in lubrication-deficient joints.