Effects of FGF-2 and FGF receptor antagonists on MMP enzymes, aggrecan, and type II collagen in primary human OA chondrocytes.

OBJECTIVES

Fibroblast growth factor (FGF)-2 is a member of the FGF family and is found in the synovial fluid of patients with osteoarthritis (OA). The aim of this study was to investigate the effects of FGF-2 on human OA cartilage/chondrocytes by examining the association between FGF-2 and the cartilage degrading enzymes matrix metalloproteinase (MMP)-1 and MMP-13 and the major cartilage matrix components aggrecan and collagen II.

METHOD: Cartilage samples were obtained from 97 OA patients undergoing total knee replacement surgery. Cartilage tissue cultures were conducted and levels of FGF-2, MMP-1, and MMP-13 released into the culture medium were measured by immunoassay. The effects of FGF-2 on the expression of MMP-1, MMP-13, aggrecan, and collagen II were further investigated in cultures of primary human OA chondrocytes.

RESULTS

FGF-2, MMP-1, and MMP-13 were released into the culture medium from cartilage samples obtained from patients with OA. FGF-2 concentrations correlated positively with the concentrations of MMP-1 (r = 0.414, p < 0.001) and MMP-13 (r = 0.362, p < 0.001). FGF-2 also up-regulated the production of MMP-1 and MMP-13, and down-regulated the expression of aggrecan and collagen II, in human OA chondrocyte cultures. Furthermore, FGF receptor antagonists AZD4547 and NVP-BGJ398 down-regulated the expression of MMP-1 and MMP-13 and up-regulated aggrecan and collagen II both in the absence and in the presence of exogenous FGF-2.

CONCLUSIONS

Our results suggest that, in contrast to its growth factor-like effects in some other tissues, FGF-2 induces catabolic effects in human OA cartilage. Moreover, FGF receptor antagonists showed promising beneficial effects on the balance of catabolic and anabolic factors within OA cartilage.