This study investigated the mechanism of direct and indirect actions of @entity10245 ( @entity10245 ) on osteoclast differentiation using two @entity19 cell culture systems. In the coculture system of osteoblasts and bone marrow cells, @entity10245 stimulated osteoclast formation. This effect was decreased markedly by @entity16323 ( @entity16323 ) or @entity8228 , a selective cyclo-oxygenase 2 (COX-2) inhibitor. @entity10245 (> or = 10(-9) M) stimulated receptor activator of nuclear factor kappaB ligand/osteoclast differentiation factor ( @entity5271 / @entity5271 ) messenger RNA (mRNA) expression from 2 h to 7 days in cultured osteoblasts. @entity8228 did not affect the early induction but decreased the later one, indicating that the later effect is mediated by COX-2 induction in osteoblasts. To study the direct action of @entity10245 on osteoclast precursors, we used @entity19 macrophage-like cell line C7 cells that can differentiate into osteoclasts in the presence of soluble @entity5271 / @entity5271 ( @entity5271 ) and @entity9827 ( @entity9827 ). Although osteoblasts expressed all FGF receptors ( @entity10824 to -4), only @entity10824 was detected in C7 cells at various differentiation stages. @entity10245 alone or in combination with sRANKL/ @entity5271 did not induce osteoclastogenesis from C7 cells; however, @entity10245 from lower concentrations (> or = 10(-11) M) significantly decreased osteoclast formation induced by @entity9827 in the presence of sRANKL/ @entity5271 . @entity10245 did not alter mRNA levels of @entity9827 receptor (Fms) or RANK in C7 cells. Immunoprecipitation/ immunoblotting analyses revealed that @entity669 phosphorylation of several cellular proteins including Fms in C7 cells induced by @entity9827 was inhibited by @entity10245 in the presence of @entity5271 . We conclude that @entity10245 regulates osteoclast differentiation through two different mechanisms: (1) an indirect stimulatory action via osteoblasts to induce @entity5271 / @entity5271 partly through COX-2 induction and @entity3009 production and (2) a direct inhibitory action on osteoclast precursors by counteracting @entity9827 signaling.

Regulation of osteoclast differentiation by @entity10245 : stimulation of receptor activator of nuclear factor kappaB ligand/osteoclast differentiation factor expression in osteoblasts and inhibition of XXXX function in osteoclast precursors.

@entity9827 :: ('12977(Tax:10090)', 'Gene') :: ['M-CSF', 'macrophage colony-stimulating factor'] @entity10245 :: ('14173(Tax:10090)', 'Gene') :: ['fibroblast growth factor 2', 'FGF-2'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity5271 :: ('21943(Tax:10090)', 'Gene') :: ['ODF', 'RANKL', 'sRANKL/ODF'] @entity3009 :: ('CHEBI:26333', 'Chemical') :: ['prostaglandin'] @entity16323 :: ('18383(Tax:10090)', 'Gene') :: ['osteoprotegerin', 'OPG'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity10824 :: ('14182(Tax:10090)', 'Gene') :: ['FGFR-1'] @entity8228 :: ('MESH:C080955', 'Chemical') :: ['NS-398']
@entity9827 :: (12977(Tax:10090),Gene) :: ['macrophage colony-stimulating factor']
