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

Objective. The glycoprotein lubricin (encoded by the gene Prg4) is secreted by surface chondrocytes and synovial cells, and has been shown to reduce friction in vitro. In contrast to man-made bearings, mammalian diarthrodial joints must endogenously produce frictionreducing agents. This study was undertaken to investigate whether friction is associated with wear.Methods. The lubricating ability of synovial fluid (SF) samples from humans with genetic lubricin deficiency was tested in vitro. The coefficient of friction in the knee joints of normal and lubricin-null mice was measured ex vivo; these joints were also studied by light and electron microscopy. Atomic force microscopy was used to image and measure how lubricin reduces friction in vitro.Results. SF lacking lubricin failed to reduce friction in the boundary mode. Joints of lubricin-null mice showed early wear and higher friction than joints from their wild-type counterparts. Lubricin self-organized and reduced the work of adhesion between apposing asperities.Conclusion. These data show that friction is coupled with wear at the cartilage surface in vivo. They imply that acquired lubricin degradation occurring in inflammatory joint diseases predisposes the cartilage to damage. Lastly, they suggest that lubricin, or similar biomolecules, will have applications in man-made devices in which reducing friction is essential.

ABSTRACT. Osteoarthritis (OA) is the most common musculoskeletal disease, affecting millions of individuals worldwide. New treatment approaches require an understanding of the pathophysiology of OA and its biomechanical, inflammatory, genetic, and environmental risk factors. The purpose of animal models of OA is to reproduce the pattern and progression of degenerative damage in a controlled fashion, so that opportunities to monitor and modulate symptoms and disease progression can be identified and new therapies developed. This review discusses the features, strengths, and weaknesses of the common animal models of OA; considerations to be taken when choosing a method for experimental induction of joint degeneration; and the challenges of measuring of OA progression and symptoms in these models.

Osteoarthritis is a complex disease involving the mechanical breakdown of articular cartilage in the presence of altered joint mechanics and chondrocyte death, but the connection between these factors is not well established. Lubricin, a mucinous glycoprotein encoded by the PRG4 gene, provides boundary lubrication in articular joints. Joint friction is elevated and accompanied by accelerated cartilage damage in humans and mice that have genetic deficiency of lubricin. Here, we investigated the relationship between coefficient of friction and chondrocyte death using ex vivo and in vitro measurements of friction and apoptosis. We observed increases in whole-joint friction and cellular apoptosis in lubricin knockout mice compared with wild-type mice. When we used an in vitro bovine explant cartilage-on-cartilage bearing system, we observed a direct correlation between coefficient of friction and chondrocyte apoptosis in the superficial layers of cartilage. In the bovine explant system, the addition of lubricin as a test lubricant significantly lowered the static coefficient of friction and number of apoptotic chondrocytes. These results demonstrate a direct connection between lubricin, boundary lubrication, and cell survival and suggest that supplementation of synovial fluid with lubricin may be an effective treatment to prevent cartilage deterioration in patients with genetic or acquired deficiency of lubricin.camptodactyly-arthropathy-coxa vara-pericarditis | shear strain | antiadhesion | tribology