Involvement of p38 mitogen-activated protein kinase signaling pathway in osteoclastogenesis mediated by receptor activator of NF-kappa B ligand (RANKL)
M. Matsumoto et al., Involvement of p38 mitogen-activated protein kinase signaling pathway in osteoclastogenesis mediated by receptor activator of NF-kappa B ligand (RANKL), J BIOL CHEM, 275(40), 2000, pp. 31155-31161
The receptor activator of NF-kappa B ligand (RANKL) induces osteoclast diff
erentiation from bone marrow cells in the presence of macrophage colony-sti
mulating 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 c
ould differentiate into osteoclastlike cells following treatment with RANKL
. In a dose-dependent manner, SB203580 but not PD98059, inhibited RANKL-ind
uced differentiation. Among three MAP kinase families tested, this inhibiti
on profile coincided only with the activation of p38 MAP kinase. Expression
in RAW264 cells of the dominant negative form of either p38 alpha MAP kina
se or MAP kinase kinase (MKK) 6 significantly inhibited RAM(L-induced diffe
rentiation of the cells, These results indicate that activation of the p38
MAP kinase pathway plays an important role in RANKL-induced osteoclast diff
erentiation of precursor bone marrow cells.