title: Serotonin acts as a novel regulator of interleukin-6 secretion in osteocytes through the activation of the 5-HT(2B) receptor and the ERK1/2 signalling pathway.
abstract: Interleukin-6 (IL-6) is a potent stimulator of osteoclastic bone resorption. Osteocyte secretion of IL-6 plays an important role in bone metabolism. Serotonin (5-HT) has recently been reported to regulate bone metabolism. The aim of this study was to evaluate the effect of serotonin on osteocyte expression of IL-6. The requirement for the 5-HT receptor(s) and the role of the extracellular signal-regulated kinase 1/2 (ERK1/2) in serotonin-induced IL-6 synthesis were examined. In this study, real-time PCR and ELISA were used to analyse IL-6 gene and protein expression in serotonin-stimulated MLO-Y4 cells. ERK1/2 pathway activation was determined by Western blot. We found that serotonin significantly activated the ERK1/2 pathway and induced IL-6 mRNA expression and protein synthesis in cultured MLO-Y4 cells. However, these effects were abolished by pre-treatment of MLO-Y4 cells with a 5-HT2B receptor antagonist, RS127445 or the ERK1/2 inhibitor, PD98059. Our results indicate that serotonin stimulates osteocyte secretion of IL-6 and that this effect is associated with activation of 5-HT2B receptor and the ERK1/2 pathway. These findings provide support for a role of serotonin in bone metabolism by indicating serotonin regulates bone remodelling by mediating an inflammatory cytokine.
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, PR China; West China College of Stomatology, Sichuan University, Chengdu 610041, PR China.
authors.forename: Xianxian
authors.initials: X
authors.lastname: Li
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ma
authors.forename: Xiangnan
authors.initials: X
authors.lastname: Wu
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Hao
authors.forename: Jian
authors.initials: J
authors.lastname: Yin
authors.forename: Jiefei
authors.initials: J
authors.lastname: Shen
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Hang
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D005419:Flavonoids / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010011:Osteocytes / Q000187:drug effects / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D044403:Receptor, Serotonin, 5-HT2B / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: D005419:Flavonoids; D015850:Interleukin-6; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D044403:Receptor, Serotonin, 5-HT2B; D058826:Serotonin 5-HT2 Receptor Agonists; D012702:Serotonin Antagonists; C121466:2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine; D012701:Serotonin; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: Extracellular signal-regulated kinase 1/2 (ERK1/2); Interleukin-6 (IL-6); Osteocytes; Serotonin (5-HT)