Mechanism of bone resorption by fibroblast growth factor-2

Fibroblast growth factor-2(FGF-2)at high and pharmacological concentrations is known to act on osteoblastic cells to indirectly stimulate osteoclastic bone resorption.In this study，we investigated the direct action of FGF-2 on mature osteoclasts using rabbit and mouse osteoclast cultures。FGF-2([greater than or equal]10-I D1-12个D 1M)exhibited stimulation on pit formation resorbed by isolated rabbit osteclasts with a maximum effect of 1.9-fold at 10个I D1-11个D 1M and no further stimulation at higher concentrations，whereas FGF-2([greater than or equal]10个D1-9个D1M)showed stimulation on pit formation resorbed by unfractionbated cells to 7-fold。FGF-2([greater than or equal]10个D1-12个D1M)also increased cathepsin K and MMP19mRNA levels in mouse osteoclasts isolated from the co-culture of marrow cells and osteoblasts.Among FGF receptors(FGFR1to4)，only FGFR1was detected on isolated mouse osteoclasts，while all FGFRs were identified on mouse osteoblasts.FGF-2(10I D1-12I D1M)up-regulated the phosphorylation of cellular proteins including p42/p44mitogen-activated protein(MAP)kinase，and increased the kinase activity of immunoprecipitated FGFR1in mouse osteoclasts.The stimulation of FGF-2 on rabbit and mouse osteoclast functions was abrogated by PD98059，a specific inhibitor of p42/p44MAP kinase。These results strongly suggest that FGF-2 acts directly on mature osteoclasts through activation of FGFR1 and p42/p44MAP kinase，causing the stimulation of bone resorption at physiological or pathological concentrations.

Fibroblast growth factor-2 (FGF-2) at high and pharmacological concentrations is known to act on osteoblastic cells to indirectly stimulate osteoclastic bone resorption. In this study, we investigated the direct action of FGF-2 on mature osteoclasts using rabbit and mouse osteoclast cultures. FGF-2 (【greater than or equal】10-ィイD1-12ィエD1 M) exhibited stimulation on pit formation resorbed by isolated rabbit osteclasts with a maximum effect of 1.9-fold at 10ィイD1-11ィエD1 M and no further stimulation at higher concentrations, whereas FGF-2(【greater than or equal】10ィイD1-9ィエD1 M) showed stimulation on pit formation resorbed by unfractionated bone cells up to 7.5-fold. FGF-2 (【greater than or equal】10ィイD1-12ィエD1 M) also increased cathepsin K and MMP19 mRNA levels in mouse osteoclasts isolated from the co-culture of marrow cells and osteoblasts. Among FGF receptors (FGFR1 to 4), only FGFR1 was detected on isolated mouse osteoclasts, while all FGFRs were identified on mouse osteoblasts. FGF-2 (10ィイD1-12ィエD1 M) up-regulated the phosphorylation of cellular proteins including p42/p44 mitogen-activated protein (MAP) kinase, and increased the kinase activity of immunoprecipitated FGFR1 in mouse osteoclasts. The stimulation of FGF-2 on rabbit and mouse osteoclast functions was abrogated by PD98059, a specific inhibitor of p42/p44 MAP kinase. These results strongly suggest that FGF-2 acts directly on mature osteoclasts through activation of FGFR1 and p42/p44 MAP kinase, causing the stimulation of bone resorption at physiological or pathological concentrations.