Postnatal expression in hyaline cartilage of constitutively active human collagenase-3 (MMP-13) induces osteoarthritis in mice

It has been suggested that increased collagenase-3 (MMP-13) activity plays a pivotal role in the pathogenesis of osteoarthritis (OA). We have used tet racycline-regulated transcription in conjunction with a cartilage-specific promoter to target a constitutively active human MMP-13 to the hyaline cart ilages and joints of transgenic mice. Postnatal expression of this transgen e resulted in pathological changes in articular cartilage of the mouse join ts similar to those observed in human OA. These included characteristic ero sion of the articular cartilage associated with loss of proteoglycan and ex cessive cleavage of type II collagen by collagenase, as well as synovial hy perplasia. These results demonstrate that excessive MMP-13 activity can res ult in articular cartilage degradation and joint pathology of the kind obse rved in OA, suggesting that excessive activity of this proteinase can lead to this disease.