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Histamine stimulates production of osteoclast differentiation factor/receptor activator of nuclear factor-kappaB
Yoshiaki Deyama1, Takashi Kikuiri, Gen ichi Ohnishi
1Division of Molecular Cell Pharmacology, Department of Oral Pathobiological Science, Graduate School of Dental Medicine, Hokkaido University, Kita 13, Nishi 7, Kita-ku, Sapporo 060-8586, Japan. dey@den.hokudai.ac.jp
Abstract:
Histamine H(1),H(2), and H(3) receptors are expressed by osteoblastic MC3T3-E1 (E1) cells derived from mouse calvaria. Expression of the osteoclast differentiation factor (ODF)/receptor activator of nuclear factor-kappaB ligand (RANKL) transcript was induced in E1 cells and bone marrow stromal cells (ST2). Histamine markedly increased the steady-state level of ODF/RANKL mRNA in a dose-dependent manner. The effect of histamine on expression of ODF/RANKL mRNA by E1 cells was transient, with a peak at 6h. Western blot analysis revealed that histamine increased production of ODF/RANKL protein by E1 cells at 12h. In cocultures of E1 cells and mouse bone marrow cells, histamine stimulated osteoclastogenesis in the presence of 1,25-dihydroxyvitamin D(3) and this effect was blocked by preincubation with neutralizing antibody against ODF/RANKL. These results suggest that histamine regulates osteoclastogenesis, at least in part, through induction of ODF/RANKL expression by osteoblasts and bone marrow stromal cells.
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