Activation of p38 mitogen-activated protein kinase is crucial in osteoclastogenesis induced by tumor necrosis factor.
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.
Matsumoto
M
M
Laboratory of Cellular Biochemistry, RIKEN (The Institute of Physical and Chemical Research) Saitama, Japan.
Sudo
T
T
Maruyama
M
M
Osada
H
H
Tsujimoto
M
M
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D015726:Giant Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D007093:Imidazoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D047908:Intracellular Signaling Peptides and Proteins; D016173:Macrophage Colony-Stimulating Factor; D008562:Membrane Glycoproteins; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011725:Pyridines; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one