Matrix metalloproteinase-13 expression in rabbit knee joint connective tissues: influence of maturation and response to injury

The hypothesis of the present work was that expression of matrix metallopro teinase-13 (MMP-13, collagenase-3) would be induced during conditions invol ving important matrix remodeling such as ligament maturation, scar healing and joint instability. Therefore, MMP-13 expression in the medial collatera l ligament (MCL) during the variable situations of tissue maturation and he aling was assessed. MMP-13 expression in three intra-articular connective t issues of the knee (i.e. articular cartilage, menisci and synovium) followi ng the transection of the anterior cruciate ligament of the knee was evalua ted at 3 and 8 weeks post-injury. MMP-13 mRNA (semi-quantitative RT-PCR) an d protein (immunohistochemistry and Western blotting) were detected in all of the tissues studied. Significantly higher :MCH, mRNA levels for MMP-13 w ere detected during the early phases of tissue maturation (i.e. 29 days in utero and 2-month-old rabbits) compared to later phases (5- and 12-month-ol d rabbits). This pattern of expression was recapitulated following MCL inju ry, with very high levels of expression in scar tissue at 3 weeks post-inju ry and then a decline to levels not significantly different from control va lues by 14 weeks. Elevated mRNA levels correlated with increased protein le vels for MMP-13 in both menisci and synovium following the transection of t he anterior cruciate ligament and during medial collateral ligament healing . These results indicate that MMP-13 expression is regulated by a number of variables and that high levels of expression occur in situations when conn ective tissue remodeling is very active. (C) 2000 Elsevier Science B.V./Int ernational Society of Matrix Biology. All rights reserved.