TGF-β1, TGF-β3, and PGE2 regulate contraction of human patellar tendon fibroblasts

To understand the role of tendon fibroblast contraction in tendon healing, we investigated the contraction of human patellar tendon fibroblasts (HPTFs) and its regulation by transforming growth factor-beta 1 (TGF-beta 1), TGF-beta 3, and prostaglandin E-2(PGE(2)). HPTFs were found to wrinkle the underlying thin silicone membranes, demonstrating that these tendon fibroblasts are contractile. Using fibroblast populated collagen gels (FPCGs), exogenous addition of TGF-beta 1 or TGF-beta 3 was found to increase fibroblast contraction compared to non-treated fibroblasts in serum-free medium, whereas PGE(2) was found to decrease the tendon fibroblast contraction. Moreover, the tendon fibroblasts in collagen gels treated with TGF-beta 1 contracted to a greater degree than those treated with TGF-beta 3. Since the extent of fibroblast contraction is related to scar tissue formation, this differential effect of TGF-beta 1 and TGF-beta 3 on HPTF contraction supports the previous finding that TGF-beta 1 induces scar tissue formation, whereas TGF-beta 3 reduces its formation. Further, the reduced tendon fibroblast contraction by PGE(2) suggests that excessive presence of this inflammatory mediator in the wound site might retard tendon healing. Taken together, the results of this study suggest that regulation of human tendon fibroblast contraction may reduce scar tissue formation and therefore improve the mechanical properties of healing tendons.