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 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.
Hellio Le Graverand
M P
MP
McCaig Center for Joint Injury and Arthritis Research, Faculty of Medicine, University of, Alberta, T2N 4N1, Calgary, Canada.
Eggerer
J
J
Sciore
P
P
Reno
C
C
Vignon
E
E
Otterness
I
I
Hart
D A
DA
D000818:Animals; D000070598:Anterior Cruciate Ligament Injuries; D001483:Base Sequence; D002358:Cartilage, Articular / Q000201:enzymology; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000235:genetics* / Q000378:metabolism*; D003238:Connective Tissue / Q000201:enzymology / Q000254:growth & development / Q000293:injuries; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D007718:Knee Injuries / Q000201:enzymology* / Q000235:genetics; D007719:Knee Joint / Q000201:enzymology* / Q000254:growth & development; D053509:Matrix Metalloproteinase 13; D017888:Medial Collateral Ligament, Knee / Q000201:enzymology / Q000254:growth & development / Q000293:injuries; D008592:Menisci, Tibial / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D013583:Synovial Membrane / Q000201:enzymology; D014945:Wound Healing / Q000235:genetics / Q000502:physiology
D017931:DNA Primers; D012333:RNA, Messenger; D003094:Collagen; D017364:Collagenases; D053509:Matrix Metalloproteinase 13