Histamine stimulates production of osteoclast differentiation factor/receptor activator of nuclear factor-kappaB ligand by osteoblasts.
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.
Deyama
Yoshiaki
Y
Division 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
Kikuiri
Takashi
T
Ohnishi
Gen ichi
Gi
Feng
Yi Gang
YG
Takeyama
Sadaaki
S
Hatta
Mitsutoki
M
Yoshimura
Yoshitaka
Y
Suzuki
Kuniaki
K
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010010:Osteoclasts / Q000502:physiology; D053245:RANK Ligand; D012333:RNA, Messenger / Q000096:biosynthesis; D053246:Receptor Activator of Nuclear Factor-kappa B; D011968:Receptors, Histamine / Q000096:biosynthesis / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism
D002352:Carrier Proteins; D006633:Histamine Antagonists; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D011968:Receptors, Histamine; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D006632:Histamine