BASIC FIBROBLAST GROWTH-FACTOR - AN AUTOCRINE GROWTH-FACTOR FOR EPIPHYSEAL GROWTH-PLATE CHONDROCYTES

Basic fibroblast growth factor (bFGF) is a permissive mitogen for cult ured chondrocytes and has been localized in the specific zones of the epiphyseal growth plate. In this study, we demonstrate that bFGF prese nt in cartilage originates from within the cellular constituents of th is tissue. Utilizing reverse transcription coupled to the polymerase c hain reaction (PCR), bFGF mRNA was found in extracts of cartilage tiss ue. Immunocytochemical studies revealed that bFGF was present intracel lularly in freshly isolated proliferative chondrocytes and in the extr acellular matrix (ECM) after 24 h of culture. Western blot analysis of protein extracts from isolated proliferative chondrocytes identified a bFGF immunoreactive species with a molecular weight of approximately 18 kDa. In situ hybridization confirmed the presence of bFGF mRNA in freshly isolated proliferative chondrocytes. The bFGF in the ECM seeme d to be sequestered and not available for biological activity, since t hese cells still required exogenous bFGF for cell proliferation. This sequestered bFGF could be released to stimulate cell proliferation whe n cultures were treated with plasmin, a proteolytic enzyme. These data support the hypothesis that bFGF is synthesized by chondrocytes and f unctions as an autocrine/paracrine mitogen via its deposition into the ECM with subsequent release from the ECM of cartilage being a critica l step in biological activity. In addition, the study provides further evidence that locally produced bFGF plays an important role in normal growth and development of cartilage tissue. (C) 1996 Wiley-Liss, Inc.