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 regu lators of their expression, mRNA levels for collagenase, stromelysin, uroki nase, 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 ad dition, 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 l evels for the cytokines iNOS and COX-2 were either unchanged or depressed e arly after injury. The results indicate that alterations in mRNA levels for proteinases and inhibitors occurring early after injury are likely being i nfluenced by factors other than IL-1, TNF, or products of COX-2 or iNOS. (C ) 1998 Academic Press.