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MC3T3-E1 骨芽細胞株におけるセロトニン5-HT2A 受容体の機能的発現(発表論文抄録(2010)) Functional expression of 5-HT2A receptor in osteoblastic MC3T3-E1 cells. Hirai, Takao Kaneshige, Kota Kurosaki, Teruko Nishio, Hiroaki Amphetamines Animals Cell Line Cell Proliferation Mice Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Osteoblasts Phosphorylation Receptor, Serotonin, 5-HT2A Serotonin 5-HT2 Receptor Antagonists Serotonin Receptor Agonists In the previous study, we reported the gene expression for proteins related to the function of 5-hydroxytryptamine (5-HT, serotonin) and elucidated the expression patterns of 5-HT(2) receptor subtypes in mouse osteoblasts. In the present study, we evaluated the possible involvement of 5-HT receptor subtypes and its inactivation system in MC3T3-E1 cells, an osteoblast cell line. DOI, a 5-HT(2A) and 5-HT(2C) receptor selective agonist, as well as 5-HT concentration-dependently increased proliferative activities of MC3T3-E1 cells in their premature period. This effect of 5-HT on cell proliferation were inhibited by ketanserin, a 5-HT(2A) receptor specific antagonist. Moreover, both DOI-induced cell proliferation and phosphorylation of ERK1 and 2 proteins were inhibited by PD98059 and U0126, selective inhibitors of MEK in a concentration-dependent manner. Furthermore, treatment with fluoxetine, a 5-HT specific re-uptake inhibitor which inactivate the function of extracellular 5-HT, significantly increased the proliferative activities of MC3T3-E1 cells in a concentration-dependent manner. Our data indicate that 5-HT fill the role for proliferation of osteoblast cells in their premature period. Notably, 5-HT(2A) receptor may be functionally expressed to regulate mechanisms underlying osteoblast cell proliferation, at least in part, through activation of ERK/MAPK pathways in MC3T3-E1 cells. In the previous study, we reported the gene expression for proteins related to the function of 5-hydroxytryptamine (5-HT, serotonin) and elucidated the expression patterns of 5-HT(2) receptor subtypes in mouse osteoblasts. In the present study, we evaluated the possible involvement of 5-HT receptor subtypes and its inactivation system in MC3T3-E1 cells, an osteoblast cell line. DOI, a 5-HT(2A) and 5-HT(2C) receptor selective agonist, as well as 5-HT concentration-dependently increased proliferative activities of MC3T3-E1 cells in their premature period. This effect of 5-HT on cell proliferation were inhibited by ketanserin, a 5-HT(2A) receptor specific antagonist. Moreover, both DOI-induced cell proliferation and phosphorylation of ERK1 and 2 proteins were inhibited by PD98059 and U0126, selective inhibitors of MEK in a concentration-dependent manner. Furthermore, treatment with fluoxetine, a 5-HT specific re-uptake inhibitor which inactivate the function of extracellular 5-HT, significantly increased the proliferative activities of MC3T3-E1 cells in a concentration-dependent manner. Our data indicate that 5-HT fill the role for proliferation of osteoblast cells in their premature period. Notably, 5-HT(2A) receptor may be functionally expressed to regulate mechanisms underlying osteoblast cell proliferation, at least in part, through activation of ERK/MAPK pathways in MC3T3-E1 cells. 福山大学薬学部 2011-12-25 eng departmental bulletin paper https://fukuyama-u.repo.nii.ac.jp/records/8847 AN10064550 0288-724X 福山大学薬学部研究年報 Annual report of the Faculty of Pharmacy & Pharmaceutical Sciences, Fukuyama University 29 59 59 https://fukuyama-u.repo.nii.ac.jp/record/8847/files/MC3T3-E1 骨芽細胞株におけるセロトニン5-HT2A 受容体の機能的発現.pdf application/pdf 613.6 kB 2018-01-15