The Journal of Orthopaedic Research

Takashi Marui, Christopher Niyibizi, Helga I. Georgescu, Min Cao, Karl W. Kavalkovich, Rebecca E. Levine, Savio L-Y. Woo


Although it has been reported that several growth factors modulate soft tissue healing, specific effects of growth factors on protein synthesis during ligament healing have not been widely investigated. In this study, we examined the effects of basic and acidic fibroblast growth factor (bFGF and aFGF), transforming growth factor ß1 (TGF-ß1), and epidermal growth factor (EGF) on collagen and non-collagenous protein synthesis by cultured fibroblasts from medial collateral ligament (MCL) and anterior cruciate ligament (ACL) in vitro. Tritiated proline uptake was used to measure collagen and non-collagenous protein synthesis, and SDS-PAGE was used to analyze the type of collagens synthesized. Our data showed that TGF-ß1 increased both collagen and non-collagenous protein synthesis by MCL and ACL fibroblasts on a dose-dependent basis. Collagen synthesis of cultured MCL and ACL fibroblasts was increased by treatment with TGF-ß1 up to approximately one-and-a-half times as much as those of untreated controls. Although the response to TGF-ß1 by ACL fibroblasts was equal to that by MCL fibroblasts, the amount of matrix proteins synthesized by ACL fibroblasts was approximately half of that by MCL fibroblasts. The increase was mostly in type I collagen. EGF treatment of ACL fibroblasts increased collagen synthesis by approximately 25%, but had little effect on MCL fibroblasts. Neither bFGF nor aFGF increased either collagen or non-collagenous protein synthesis. These findings suggest that topical application of TGF-ß1, alone or in combination with EGF, may have the potential to strengthen the ligaments by increasing matrix synthesis during its remodeling and healing process.