Temporal alterations in mRNA levels for proteinases and inhibitors and their potential regulators in the healing medial collateral ligament.
Wound healing in ligaments is a complex process which leads to functionally impaired scar tissue, even after extended time postinjury. To investigate the potential role of proteinases and inhibitors, as well as potential regulators of their expression, mRNA levels for collagenase, stromelysin, urokinase, PAI-1, and TIMPs 1 to 4 have been assessed by semiquantitative RT-PCR in RNA isolated from rabbit ligaments 3, 6, and 14 weeks postinjury. In addition, mRNA levels for IL-1, TNF, COX-2, and iNOS, potential regulators of proteinase/inhibitor expression, have been assessed. mRNA levels for the proteinases TIMP-1, -2, and -3 and PAI-1 were elevated early in scar tissue, but TIMP-4 mRNA levels exhibited a different pattern. In contrast, mRNA levels for the cytokines iNOS and COX-2 were either unchanged or depressed early after injury. The results indicate that alterations in mRNA levels for proteinases and inhibitors occurring early after injury are likely being influenced by factors other than IL-1, TNF, or products of COX-2 or iNOS.
Reno
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MaCaig Center for Joint Injury and Arthritis Research, Faculty of Medicine, University of Calgary, Alberta, T2N 4N1, Canada.
Boykiw
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Martinez
M L
ML
Hart
D A
DA
D000818:Animals; D017364:Collagenases / Q000235:genetics / Q000378:metabolism; D017885:Collateral Ligaments / Q000201:enzymology* / Q000293:injuries*; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011817:Rabbits; D015842:Serine Proteinase Inhibitors / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics
D016207:Cytokines; D007527:Isoenzymes; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D014568:Urokinase-Type Plasminogen Activator; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3