RRC ID 61771
Author Matsumoto M, Sudo T, Saito T, Osada H, Tsujimoto M.
Title Involvement of p38 mitogen-activated protein kinase signaling pathway in osteoclastogenesis mediated by receptor activator of NF-kappa B ligand (RANKL).
Journal J Biol Chem
Abstract The receptor activator of NF-kappaB ligand (RANKL) induces osteoclast differentiation from bone marrow cells in the presence of macrophage colony-stimulating factor. We found that treatment of bone marrow cells with SB203580 inhibited osteoclast differentiation via inhibition of the RANKL-mediated signaling pathway. To elucidate the role of p38 mitogen-activated protein (MAP) kinase pathway in osteoclastogenesis, we employed RAW264 cells which could differentiate into osteoclast-like cells following treatment with RANKL. In a dose-dependent manner, SB203580 but not PD98059, inhibited RANKL-induced differentiation. Among three MAP kinase families tested, this inhibition profile coincided only with the activation of p38 MAP kinase. Expression in RAW264 cells of the dominant negative form of either p38alpha MAP kinase or MAP kinase kinase (MKK) 6 significantly inhibited RANKL-induced differentiation of the cells. These results indicate that activation of the p38 MAP kinase pathway plays an important role in RANKL-induced osteoclast differentiation of precursor bone marrow cells.
Volume 275(40)
Pages 31155-61
Published 2000-10-6
DOI 10.1074/jbc.M001229200
PII M001229200
PMID 10859303
MeSH Animals Blotting, Western Bone Marrow Cells / drug effects Calcium-Calmodulin-Dependent Protein Kinases / genetics Calcium-Calmodulin-Dependent Protein Kinases / metabolism Carrier Proteins / metabolism* Cell Differentiation / drug effects Dose-Response Relationship, Drug Enzyme Activation Enzyme Inhibitors / pharmacology Flavonoids / pharmacology Genes, Dominant Imidazoles / pharmacology JNK Mitogen-Activated Protein Kinases* MAP Kinase Kinase 4 MAP Kinase Kinase 6 Macrophage Colony-Stimulating Factor / metabolism Membrane Glycoproteins / metabolism* Mice Mitogen-Activated Protein Kinase Kinases / metabolism Mitogen-Activated Protein Kinases / genetics Mitogen-Activated Protein Kinases / metabolism* Osteoclasts / metabolism Osteoclasts / physiology* Pyridines / pharmacology RANK Ligand RNA, Messenger / metabolism Receptor Activator of Nuclear Factor-kappa B Retroviridae / metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Time Factors p38 Mitogen-Activated Protein Kinases
IF 4.238
Human and Animal Cells RAW 264(RCB0535)