Effect of growth factors on matrix synthesis by ligament fibroblasts

Abstract

Although it has been reported that several growth factors modulate soft-tissue healing, the 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 factors, transforming growth factor beta 1, and epidermal growth factor on collagen and noncollagenous protein synthesis by cultured fibroblasts from medial collateral ligament and anterior cruciate ligament in vitro. Uptake of tritiated proline was used to measure synthesis of collagen and noncollagenous protein, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to analyze the type of collagens synthesized. Our data showed that transforming growth factor beta 1 increased both collagen and noncollagenous protein synthesis by medial collateral and anterior cruciate ligament fibroblasts on a dose-dependent basis. Collagen synthesis by cultured fibroblasts from the medial collateral and anterior cruciate ligaments was increased by treatment with transforming growth factor beta 1 by as much as approximately 1.5 times that of untreated controls. Although the response to transforming growth factor beta 1 by anterior cruciate ligament fibroblasts was equal to that by medial collateral ligament fibroblasts, the amounts of matrix proteins synthesized by anterior cruciate ligament fibroblasts were approximately half of that by medial collateral ligament fibroblasts. The increase was mostly in type-I collagen. Treatment of anterior cruciate ligament fibroblasts with epidermal growth factor increased collagen synthesis by approximately 25% but had little effect on medial collateral ligament fibroblasts. Neither basic nor acidic fibroblast growth factor increased either collagen or noncollagenous protein synthesis. These findings suggest that topical application of transforming growth factor beta 1, alone or in combination with epidermal growth factor, may have the potential to strengthen the ligament by increasing matrix synthesis during its remodeling and healing processes.

Anterior cruciate ligament-derived cells have high chondrogenic potential

“…Remodeling and maintenance of ligament tissues are influenced by several factors including cellular response, ECM structure, vascularization, and growth factors [21,22]. However, the difference in chondrogenic property between ACL-and MCL-derived cells has not been elucidated.…”

Mechanoregulation of gene expression in fibroblasts

“…Increase in collagen synthesis by TGF-β1 has been shown in ligament fibroblasts previously (DesRosiers et al, 1996;Marui et al, 1997). The TGF-β1 intracellular signaling occurs via serine/threonine kinases that phosphorylate downstream-mediator, a family of SMAD proteins.…”

Ultrasound stimulation of types I and III collagen expression of tendon cell and upregulation of transforming growth factor β

“…11 It stimulates production of matrix molecules such as collagen and fibronectin from several fibroblast cell lines of human, mouse, rat, and chicken origin. [12][13][14][15] TGF-b is known to play a prominent role in the healing process of injured tendon or ligament 16,17 by directing the fibroblast migration and secretion of extracellular matrix proteins. 18 It was demonstrated that pulsed ultrasound exposure could enhance the TGF-b secretion of osteoblasts.…”