Increased expression of metalloproteinase-8 and -13 on articular cartilage in a rat immobilized knee model.

摘要

Joint immobilization is commonly used for the treatment of joint injuries and diseases, but it also causes cartilage degeneration. Damage to the fibrillar meshwork of type II collagen in the articular cartilage is a critical event for cartilage degeneration. Collagenases such as matrix metalloproteinase (MMP)-8 and MMP-13 have been considered the main enzymes responsible for the degradation of type II collagen. However, the mechanism of the articular cartilage degeneration after immobilization has not been revealed. The purpose of this study was to examine changes of the expression patterns of MMP-8 and MMP-13 after rigid immobilization of the knee joint. The unilateral knee joints of adult male rats were rigidly immobilized at 150 degrees of flexion using an internal fixator. Histological sections from the medial midcondylar region of the knee were obtained and evaluated in 3 specific areas (non-contact, transitional, and contact areas). The expression of MMP-8 and MMP-13 was evaluated by in situ hybridization. Total RNA was extracted from the articular cartilage in the contact area, and expression levels of MMP-8 and MMP-13 mRNAs were measured by quantitative real-time polymerase chain reaction. Localization of MMP-13 expression was also examined by immunohistochemistry. The expression of MMP-8 mRNA was decreased by 1 week after immobilization. After 4-week immobilization, hypertrophic differentiated chondrocytes were observed in the transitional and contact areas, and the expression of MMP-8 and MMP-13 mRNAs was increased in the chondrocytes. Rigid immobilization is associated with the increased expression of MMP-8 and MMP-13 in the hypertrophic differentiated chondrocytes. These two collagenases may play an important role in the articular cartilage degeneration after joint immobilization.