title: Modulation of osteoblast differentiation and bone mass by 5-HT2A receptor signaling in mice.
abstract: Recent studies reported that serotonin (5-hydroxytryptamine, 5-HT) may be an endogenous paracrine and/or autocrine factor that is used for intercellular communication in bone cells and between multiple organs regulating bone homeostasis. In the present study, we showed that the administration of MDL11939, a selective 5-HT2A receptor antagonist, reduced bone mass in mice. The loss of bone mass in MDL11939-treated mice was associated with impaired bone formation in vivo, as demonstrated by the lower expression of osterix (Osx) and osteocalcin than that in vehicle-treated mice. On the other hand, no significant differences were observed in osteoclast numbers between MDL11939- and vehicle-treated mice. The pharmacological blockade of 5-HT2A receptor signaling significantly decreased alkaline phosphatase activity in osteoblastic cells. In addition, the knockdown of the 5-HT2A receptor by a siRNA treatment decreased Osx, but not Runx2 gene expression in MC3T3-E1 cells. These results suggest that 5-HT2A receptor signaling mediated bone mass by regulating osteoblast differentiation.
authors.affiliation: Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Aichi, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Aichi, Japan. Electronic address: t-hirai@dpc.agu.ac.jp.
authors.forename: Takao
authors.initials: T
authors.lastname: Hirai
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Science, Yokohama College of Pharmacy, 601 Matano-cho, Totsuka-Ku, Yokohama, Kanagawa 245-0066, Japan; Division of Development Higher Brain Functions (University of Fukui), United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine, Chiba University and University of Fukui, Fukui, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ishibashi
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Science, Yokohama College of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama, Kanagawa 245-0066, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Izumo
authors.affiliation: Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Aichi, Japan. Electronic address: togariaf@dpc.agu.ac.jp.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Togari
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D005269:Femur / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D058830:Serotonin 5-HT2 Receptor Antagonists; C066169:alpha-phenyl-1-(2-phenylethyl)-4-piperidinemethanol
keywords: 5-HT(2A) receptor; Bone formation; Bone mass; Osteoblast differentiation; Osterix; Serotonin