TGF-?1, TGF-?3, and PGE2 regulate contraction of human patellar tendon fibroblasts

Abstract

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-beta1 (TGF-beta1), TGF-beta3, 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-beta1 or TGF-beta3 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-beta1 contracted to a greater degree than those treated with TGF-beta3. Since the extent of fibroblast contraction is related to scar tissue formation, this differential effect of TGF-beta1 and TGF-beta3 on HPTF contraction supports the previous finding that TGF-beta1 induces scar tissue formation, whereas TGF-beta3 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.

Mechanobiology of tendon

“…It was found that tendon and skin fibroblasts exhibited different patterns of contraction, where tendon fibroblasts produced a lower maximum contraction force than skin fibroblasts (Eastwood et al, 1996). Recent studies from our laboratory demonstrated that HPTFs in collagen gels produced an average contraction of 0.2 nN/cell , and that TGF-b1 and TGF-b3 differentially regulated the tendon fibroblast contraction (Campbell et al, 2004).…”

Cell traction force and measurement methods

“…Additionally, recent studies have found that TGF-β1 and TGF-β3, two isoforms of TGF-β, induce differential α-SMA expression and myofibroblast traction force. For instance, TGF-β1 induces higher α-SMA expression and traction force than TGF-β3 in human patellar tendon fibroblasts (Campbell et al 2004). On the other hand, soluble factors such as bFGF, PGE 2 , and γ -interferon inhibit TGF-β1-upregulated α-SMA expression and thus likely cause the downregulation of CTF (Burgess et al 2005;Hjelmeland et al 2004;Kawai-Kowase et al 2004;Kolodsick et al 2003).…”

Tendon: Biology, Biomechanics, Repair, Growth Factors, and Evolving Treatment Options

“…43,44 Transforming growth factor-␤ also serves to regulate the synthesis of collagen in tendon mechanically during physical exercise. 45 During the initial repair process and the inflammatory phase, upregulation of growth factors and cytokines such as insulin-like growth factor-1 (IGF-1) stimulate the migration and proliferation of fibroblasts and inflammatory cells to the wound site.…”