Effect of growth factors on the proliferation of fibroblasts from the medial collateral and anterior cruciate ligaments

Abstract

Growth factors have been shown to stimulate fibroblast division and thus may influence ligament healing. We analyzed the effects of individual growth factors on the proliferation of fibroblasts from the medial collateral and anterior cruciate ligaments of the rabbit in vitro in order to identify growth factors that might enhance proliferation of fibroblasts and to compare the responses of the fibroblasts from the two ligaments to these growth factors. Through measurement of the uptake of [3H]-thymidine into DNA, fibroblasts from these ligaments that had been treated with epidermal growth factor and basic fibroblast growth factor were found to proliferate nearly eight times more than control fibroblasts. Additionally, the fibroblasts of both ligaments proliferated at similar rates when exposed to platelet-derived growth factor-AA, platelet-derived growth factor-BB, basic fibroblast growth factor, insulin-like growth factor-1, and interleukin-1-alpha. However, epidermal growth factor and transforming growth factor-beta caused the fibroblasts from the medial collateral ligament to proliferate at a rate 1.3-1.4 times greater than that of fibroblasts from the anterior cruciate ligament. The reverse was true with acidic fibroblast growth factor, which stimulated the fibroblasts from the anterior cruciate ligament to proliferate at a rate 1.3-1.6 times greater than that of fibroblasts from the medial collateral ligament. This study demonstrated that growth factors can stimulate cell division in ligaments and may be effective in enhancing ligament healing but that these differences were not great enough to explain fully the clinical differences observed between healing of the medial collateral and anterior cruciate ligaments.

Effect of cyclic strain and plating matrix on cell proliferation and integrin expression by ligament fibroblasts

“…7,32 With avian tendon cells, however, synergistic action of both load and PDGF is required for enhancement of cellular proliferation. 33 Several cytokines have been shown to stimulate cell proliferation [34][35][36][37][38] and cell migration 35 of ACL and MCL cells. MCL fibroblasts have been shown to proliferate more rapidly than ACL cells when grown on tissue culture polystyrene, 29 which was confirmed in this study.…”

Anterior cruciate ligament-derived cells have high chondrogenic potential

“…Fusiform and spheroid cells packaged in the ligament-to-bone interface can produce a cartilage specific extracellular matrix (ECM), type II collagen [4]. ACL fibroblasts show lower proliferation and migration potential compared with MCL fibroblasts [4][5][6].…”

Collagen expression and biomechanical response to human recombinant transforming growth factor beta (rhTGF‐β2) in the healing rabbit MCL

“…The proliferative and synthetic response of medial collateral (MCL) and anterior cruciate ligament (ACL) fibroblasts to growth factors, including rhTGF-P2, in vitro demonstrated significant effects, however, the fibroblasts from each ligament possess unique differences [1,12,13,18,19,25,26,30,[33][34][35]44,45,48,49,60]. Furthermore, in vitro models have identified the appearance of these growth factors in healing ligaments [16,31,37,38,461.…”