title: A comparative study of histamine activities on differentiation of osteoblasts and osteoclasts.
abstract: The effects of histamine and its receptor antagonists on mouse bone marrow cells (MBMC) and MC3T3-E1 cells were studied to elucidate the precise molecular mechanisms underlying histamine activities in the respective cell types. The studied parameters were osteoclast differentiation and expressions of receptor activator of nuclear factor kappaB ligand (RANKL), histamine receptors (HR), and osteoblast differentiation markers. The osteoclastogenesis was assessed by TRAP-dye method. Expressions of RANKL, HR and the osteoblast differentiation markers were evaluated by RT-PCR analysis. In MBMC, 1 microM histamine doubled the number of osteoclast-like cells in a dose-dependent manner. Expressions of RANKL peaked at histamine concentrations of 1 microM and 0.1 microM in MBMC and MC3T3-E1, respectively. H(1)R antagonist, but not H(2)R antagonist, inhibited RANKL expressions induced by histamine in MC3T3-E1. Histamine induced expressions of cell differentiation markers in MC3T3-E1, but not in MBMC, under the conditions that RANKL expressions were induced by histamine in both types of cells. These results indicate the following: (1) Histamine induction of osteoclastogenesis is mediated by RANKL expressed via H(1)R, but not via H(2)R in mouse osteoblast-like cells; (2) and the major target of histamine action is the RANKL-RANK signaling pathway in osteocytes. This observation is consistent with the traditionally recognized histamine action of bone resorption at the osteoclast site.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Ikawa
authors.forename: Taeko
authors.initials: T
authors.lastname: Yonekawa
authors.forename: Yukie
authors.initials: Y
authors.lastname: Ohkuni
authors.forename: Mariko
authors.initials: M
authors.lastname: Kuribayashi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Fukino
authors.forename: Koichi
authors.initials: K
authors.lastname: Ueno
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002927:Cimetidine / Q000494:pharmacology; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006632:Histamine / Q000378:metabolism*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D011738:Pyrilamine / Q000494:pharmacology; D053245:RANK Ligand / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D053245:RANK Ligand; D012333:RNA, Messenger; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; C505689:Tnfsf11 protein, mouse; D016212:Transforming Growth Factor beta; D002927:Cimetidine; D006632:Histamine; C510878:ALPL protein, mouse; D000469:Alkaline Phosphatase; D011738:Pyrilamine