Regulation of osteoblast, chondrocyte, and osteoclast functions by fibroblast growth factor (FGF)-18 in comparison with FGF-2 and FGF-10

J Biol Chem. 2002 Mar 1;277(9):7493-500. doi: 10.1074/jbc.M108653200. Epub 2001 Dec 11.

Abstract

This study investigated the actions of fibroblast growth factor (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 MC3T3-E1 cells, primary chondrocytes, and prechondrocytic ATDC5 cells, although it inhibited the differentiation and matrix synthesis of these cells. FGF-18 up-regulated the phosphorylation of extracellular signal-regulated kinase in both osteoblasts and chondrocytes and up-regulated the phosphorylation of p38 mitogen-activated protein kinase only in chondrocytes. FGF-18 mitogenic actions were blocked by a specific inhibitor of extracellular signal-regulated kinase in both osteoblasts and chondrocytes and by a specific inhibitor of p38 mitogen-activated protein kinase in chondrocytes. With regard to the action of FGF-18 on bone resorption, FGF-18 not only induced osteoclast formation through receptor activator of nuclear factor-kappaB 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 for the action of FGF-2 on bone and cartilage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Bone and Bones / metabolism
  • Cartilage / metabolism
  • Cell Differentiation
  • Cell Division
  • Cell Line
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Chondrocytes / metabolism*
  • Coculture Techniques
  • Coloring Agents / pharmacology
  • Cyclooxygenase 2
  • Dose-Response Relationship, Drug
  • Fibroblast Growth Factor 10
  • Fibroblast Growth Factor 2 / metabolism*
  • Fibroblast Growth Factors / metabolism*
  • Fibroblast Growth Factors / pharmacology
  • Isoenzymes / metabolism
  • Ligands
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Osteoblasts / metabolism*
  • Osteoclasts / metabolism*
  • Phosphorylation
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Protein Binding
  • Rats
  • Signal Transduction
  • Time Factors
  • Tyrosine / metabolism
  • Up-Regulation
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Coloring Agents
  • Fgf10 protein, mouse
  • Fgf10 protein, rat
  • Fibroblast Growth Factor 10
  • Isoenzymes
  • Ligands
  • NF-kappa B
  • fibroblast growth factor 18
  • Fibroblast Growth Factor 2
  • Tyrosine
  • Fibroblast Growth Factors
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases