Influence of IGF-1, TGF-β1 and bFGF on Gene Expression in Cruciate Ligament and Dermal Fibroblasts

Fibroblasts produce extracellular matrix (ECM), secrete proteolytic enzymes, their inhibitors, cytokines and growth factors. Their secretory profile varies depending on the organ from which they originate. We previously described the influence of cartilage interstitial fluid (CIF) on the gene expression of ECM proteins, cytokines, metalloproteases and their inhibitors in synovial membrane cells, dermal (DFs) and cruciate ligament fibroblasts (CTLs). In this work we studied the reaction of rat dermal and cruciate ligament fibroblasts to the most abundant CIF cytokines: basic fibroblast growth factor (bFGF), transforming growth factor-beta 1 (TGF-beta 1) and insulin-like growth factor-1 (IGF-1) used in different combinations. The results disclosed several differences in the response of both types of fibroblast to the tested cytokines. For example IGF-1/TGF-beta 1/bFGF triplet stimulated stronger expression of hyaluronan synthases 1 and 2 (Has1 and Has2) in ligament than dermal fibroblasts. Stronger lubricin (Prg4) expression was stimulated by IGF-1/TGF-beta 1 in cruciate ligament than in dermal fibroblasts. Both combinations of cytokines stimulated Tgfb1, tissue inhibitor of metalloproteinases 1 (Timp1), inhibited tumor necrosis factor (Tnf) and metalloproteinase 3 (Mmp3) expression in both types of cells. Because fibroblasts produce different factors in response to the same stimuli, our results provide a better understanding of their role in physiological and pathological processes.