Activation of p38 mitogen-activated protein kinase is crucial in osteoclastogenesis induced by tumor necrosis factor

FEBS Lett. 2000 Dec 1;486(1):23-8. doi: 10.1016/s0014-5793(00)02231-6.

Abstract

Tumor necrosis factor (TNF) induces osteoclast differentiation from bone marrow cells in the presence of macrophage colony-stimulating factor. Treatment of bone marrow cells with SB203580 but not PD98059 inhibited TNF-induced osteoclast differentiation. In RAW264 cells which differentiate into osteoclast-like multinucleated cells by TNF treatment alone, activation of p38 mitogen-activated protein (MAP) kinase induced by murine TNF was comparable to and independent of the receptor activator of necrosis factor-kappaB ligand. Moreover, the number of multinucleated osteoclasts induced by TNF in bone marrow cell cultures derived from p38 MAP kinase gene deficient mice was significantly less than that from control mice. These results indicate that the p38 MAP kinase pathway plays a crucial role in TNF-mediated osteoclast differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / enzymology
  • Carrier Proteins / pharmacology
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Nucleus / drug effects
  • Cells, Cultured
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Giant Cells / cytology
  • Giant Cells / drug effects
  • Giant Cells / enzymology
  • Imidazoles / pharmacology
  • Intracellular Signaling Peptides and Proteins
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Membrane Glycoproteins / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / deficiency
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / enzymology
  • Osteoclasts / cytology*
  • Osteoclasts / drug effects*
  • Osteoclasts / enzymology
  • Protein-Serine-Threonine Kinases / metabolism
  • Pyridines / pharmacology
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Solubility
  • Tumor Necrosis Factor-alpha / pharmacology*
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Carrier Proteins
  • Enzyme Inhibitors
  • Flavonoids
  • Imidazoles
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Pyridines
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Tnfrsf11a protein, mouse
  • Tnfsf11 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Macrophage Colony-Stimulating Factor
  • MAP-kinase-activated kinase 2
  • Protein-Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one