Mechanism of regulation of bone and cartilage metabolism by fibroblast growth factor-18 (FGF-18)

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This study investigated the actions of FGF-18, a novel member of the FGF family on osteoblasts, chondrocytes and osteoclasts, and compared them with those of FGF-2 and FGF-10. FGF-18 stimulated the proliferation of cultured mouse primary osteoblasts, osteoblastic cell line MC3T3-E1 cells, primary chondrocytes and prechondrocytic cell line ATDC5 cells, although it inhibited the differentiation and matrix synthesis of these cells. FGF-18 up-regulated the phosphorylation of extracellular signal-regulated kinase (ERK) both in osteoblasts and chondrocytes, and p38 mitogen-activated protein kinase (MAPK) only in chondrocytes. FGF-18 mitogenic actions were blocked by a specific inhibitor of ERK in both cells, and by that of p38 MAPK in chondrocytes. Regarding the action of FGF-18 on bone resorption, FGF-18 not only induced osteoclast formation through receptor activator of NF-κB ligand and cyclooxygenase-2, but also stimulated osteoclast function to form resorbed pits on a dentine slice in the mouse coculture system. All these effects of FGF-18 bore a close resemblance to those of FGF-2, whereas FGF-10 affects none of these cells. FGF-18 may therefore compensate the action of FGF-2 on bone and cartilage.