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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.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2013 Nov 29; Vol. 441 (4), pp. 809-14. Date of Electronic Publication: 2013 Nov 05. - Publication Year :
- 2013
-
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.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cell Line
Flavonoids pharmacology
MAP Kinase Signaling System
Mice
Mitogen-Activated Protein Kinase 1 antagonists & inhibitors
Mitogen-Activated Protein Kinase 3 antagonists & inhibitors
Osteocytes drug effects
Protein Kinase Inhibitors pharmacology
Pyrimidines pharmacology
Serotonin pharmacology
Serotonin 5-HT2 Receptor Agonists pharmacology
Serotonin Antagonists pharmacology
Interleukin-6 metabolism
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 3 metabolism
Osteocytes metabolism
Receptor, Serotonin, 5-HT2B metabolism
Serotonin physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 441
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 24211588
- Full Text :
- https://doi.org/10.1016/j.bbrc.2013.10.141