TGF-β1 Decreases Plasmin-Mediated MMP Activity in Flexor Tendon Cells: Implications for Scarless Tendon Repair

Introduction Flexor tendon injuries caused by deep lacerations to the hands are a challenging problem for tissue engineers. Such injuries often result in debilitating adhesions, scar tissue that prevents the normal gliding motion of the flexor tendons through their lubricating synovial sheaths, preventing the hands from opening and closing. Evidence exists that tendon adhesions as well as scarring throughout the body are largely mediated by the pleiotropic growth factor, TGF-β1 [1], the effects of which are poorly understood in tendon. Using an in vitro model of tendon healing, we previously found that TGFβ1 causes gene expression changes in tenocytes that are consistent with scar tissue and adhesion formation [2], and upregulates the anti-fibrinolytic protein, PAI-1. Therefore, we hypothesized that TGF-β1 contributes to scarring and adhesions by reducing MMP activity through suppression of plasminogen-mediated activation by PAI1. In this study, we used our in vitro tendon-healing model to examine the effects of TGF-β1 on the expression and activation of gelatinases and their activity regulators.