Modulation of osteoblast differentiation and bone mass by 5-HT2A receptor signaling in mice

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 MDL...

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Bibliographic Details
Published in:European journal of pharmacology 2015-09, Vol.762, p.150-157
Main Authors: Tanaka, Kenjiro, Hirai, Takao, Ishibashi, Yukiko, Izumo, Nobuo, Togari, Akifumi
Format: Article
Language:English
Subjects:
3T3 Cells
5-HT2A receptor
Animals
Bone formation
Bone mass
Cell Differentiation - drug effects
Femur - cytology
Femur - drug effects
Femur - growth & development
Femur - metabolism
Gene Expression Regulation - drug effects
Male
Mice
Mice, Inbred C57BL
Organ Size - drug effects
Osteoblast differentiation
Osteoblasts - cytology
Osteoblasts - drug effects
Osteogenesis - drug effects
Osterix
Piperidines - pharmacology
Receptor, Serotonin, 5-HT2A - metabolism
Serotonin
Serotonin 5-HT2 Receptor Antagonists - pharmacology
Signal Transduction - drug effects
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Summary: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.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2015.05.048