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

• Published in: Matrix biology 2000-09, Vol.19 (5), p.431-441
• Main Authors: Hellio Le Graverand, Marie-Pierre, Eggerer, Jonna, Sciore, Paul, Reno, Carol, Vignon, Eric, Otterness, Ivan, Hart, David A
• Format: Article
• Language: English
• Subjects: Animals; Anterior Cruciate Ligament Injuries; Base Sequence; Cartilage, Articular - enzymology; Collagen - metabolism; Collagenases - genetics; Collagenases - metabolism; Connective tissue; Connective Tissue - enzymology; Connective Tissue - growth & development; Connective Tissue - injuries; DNA Primers - genetics; Female; Gene Expression; Injury models; Knee Injuries - enzymology; Knee Injuries - genetics; Knee Joint - enzymology; Knee Joint - growth & development; Ligament maturation; Matrix Metalloproteinase 13; Matrix remodeling; Medial Collateral Ligament, Knee - enzymology; Medial Collateral Ligament, Knee - growth & development; Medial Collateral Ligament, Knee - injuries; Menisci, Tibial - enzymology; MMP-13; Rabbits; RNA, Messenger - genetics; RNA, Messenger - metabolism; Synovial Membrane - enzymology; Wound Healing - genetics; Wound Healing - physiology
• ISSN: 0945-053X; 1569-1802
• DOI: 10.1016/S0945-053X(00)00093-7

The hypothesis of the present work was that expression of matrix metalloproteinase-13 (MMP-13, collagenase-3) would be induced during conditions involving important matrix remodeling such as ligament maturation, scar healing and joint instability. Therefore, MMP-13 expression in the medial collateral ligament (MCL) during the variable situations of tissue maturation and healing was assessed. MMP-13 expression in three intra-articular connective tissues of the knee (i.e. articular cartilage, menisci and synovium) following the transection of the anterior cruciate ligament of the knee was evaluated at 3 and 8 weeks post-injury. MMP-13 mRNA (semi-quantitative RT-PCR) and protein (immunohistochemistry and Western blotting) were detected in all of the tissues studied. Significantly higher MCL mRNA levels for MMP-13 were 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-old rabbits). This pattern of expression was recapitulated following MCL injury, with very high levels of expression in scar tissue at 3 weeks post-injury and then a decline to levels not significantly different from control values by 14 weeks. Elevated mRNA levels correlated with increased protein levels for MMP-13 in both menisci and synovium following the transection of the 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 connective tissue remodeling is very active.