Results. SF lubricin concentrations were significantly (P < 0.001) reduced at an early stage following ACL injury when compared with those in the contralateral joint. Within 12 months, the lubricin concentration in the injured knee (slope ؍ 0.006, SE ؍ 0.00010, P < 0.001) approached that in the contralateral knee, which did not change with time (slope ؍ ؊0.0002, SE ؍ 0.00050, P ؍ 0.71). TNF␣ levels showed a significant negative relationship with log 2 lubricin levels. IL-1, TNF␣, IL-6, procathepsin B, and neutrophil elastase concentrations in SF from injured knees were greater in samples from recently injured knees compared with those that were chronically injured. There were no detectable cytokines or enzymes in the SF of contralateral joints. Concentrations of sGAG were significantly (P ؍ 0.0002) higher in the SF from injured knees compared with the contralateral joints.Conclusion. The decrease in SF lubricin concentrations following ACL injury may place the joint at an increased risk of wear-induced damage as a consequence of lack of boundary lubrication, potentially leading to secondary osteoarthritis. The decrease in SF lubricin was associated with an increase in levels of inflammatory cytokines.Lubricin (also known as superficial zone protein or PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone articular chondrocytes (1-3). Lubricin is partly responsible for the lubrication of apposed and pressurized cartilage surfaces (4). It provides essential chondroprotective properties to articular cartilage, as evidenced by lack of cartilage surface integrity and surface disruption in PRG4-knockout mice (5). Previously, we have demonstrated decreased synovial fluid (SF) lubricating properties, indicative of decreased SF lubricin concentrations, in patients diagnosed as having traumatic synovitis (6). Altered joint mechanics lead to decreased lubricin expression in the superficial layer and decreased lubricin coating of the surface of articular cartilage, as shown in a sheep meniscectomy model (7). Lubricin expression is down-regulated by proinflammatory cytokines (e.g., interleukin-1 [IL-1], tumor necrosis factor ␣ [TNF␣], and IL-6) (8-10). Moreover, lubricin has been shown to be proteolytically susceptible to the effects of cysteine