Prg4 (proteoglycan 4 (megakaryocyte stimulating factor, articular superficial zone protein)) plays a protective role against osteoarthritis (OA). The PRG4 protein provides synovial fluid with the ability to dissipate strain energy under load, protecting bones of the joint, and also inhibits transcriptional programs that promote cartilage catabolism and hypertrophy.
These transgenic mice express the mouse Prg4 under the regulatory control of the cartilage-specific mouse Col2a1 (collagen, type II, alpha 1) promoter. PRG4 is expressed ectopically in growth plate cartilage and overexpressed in articular cartilage throughout development and adulthood. Long-term expression does not adversely affect skeletal development but protects from developing signs of age-related OA. Protective effects are also seen in models of posttraumatic OA created by cruciate ligament transection. Wildtype FVB/N mice develop changes consistent with moderate OA by 10 months of age (OARSI grade 3.5), but Prg4 transgenic animals show less severe signs of OA at the same age (OARSI grade 2). Whereas wildtype mice show increased expression of Col10a1 and Mmp13 (markers of cartilage hypertrophy and degradation), they do not show a qualitative increases in non-calcified regions of articular cartilage in the transgenic mice. Wildtype mice show a decrease in articular cartilage volume as well as in the bone area covered by cartilage, but transgenic mice show preservation of articular cartilage volumes and surface area. This model suggests a new disease-altering therapy for osteoarthritis.
