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Serotonin 2B Receptor (5-HT(2B) R) Signals through Prostacyclin and PPAR-ß/δ in Osteoblasts

Osteoporosis is due to an imbalance between decreased bone formation by osteoblasts and increased resorption by osteoclasts. Deciphering factors controlling bone formation is therefore of utmost importance for the understanding and the treatment of osteoporosis. Our previous in vivo results showed t...

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Autores principales: Chabbi-Achengli, Yasmine, Launay, Jean-Marie, Maroteaux, Luc, de Vernejoul, Marie Christine, Collet, Corinne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775737/
https://www.ncbi.nlm.nih.gov/pubmed/24069449
http://dx.doi.org/10.1371/journal.pone.0075783
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author Chabbi-Achengli, Yasmine
Launay, Jean-Marie
Maroteaux, Luc
de Vernejoul, Marie Christine
Collet, Corinne
author_facet Chabbi-Achengli, Yasmine
Launay, Jean-Marie
Maroteaux, Luc
de Vernejoul, Marie Christine
Collet, Corinne
author_sort Chabbi-Achengli, Yasmine
collection PubMed
description Osteoporosis is due to an imbalance between decreased bone formation by osteoblasts and increased resorption by osteoclasts. Deciphering factors controlling bone formation is therefore of utmost importance for the understanding and the treatment of osteoporosis. Our previous in vivo results showed that bone formation is reduced in the absence of the serotonin receptor 5-HT(2B), causing impaired osteoblast proliferation, recruitment, and matrix mineralization. In this study, we investigated the signaling pathways responsible for the osteoblast defect in 5-HT(2B)R(−/−) mice. Notably, we investigated the phospholipase A2 pathway and synthesis of eicosanoids in 5-HT(2B)R(−/−) compared to wild type (WT) osteoblasts. Compared to control osteoblasts, the lack of 5-HT(2B) receptors was only associated with a 10-fold over-production of prostacyclin (PGI(2)). Also, a specific prostacyclin synthase inhibitor (U51605) rescued totally osteoblast aggregation and matrix mineralization in the 5-HT(2B)R(−/−) osteoblasts without having any effect on WT osteoblasts. Prostacyclin is the endogenous ligand of the nuclear peroxisome proliferator activated receptor ß/δ (PPAR-ß/δ), and its inhibition in 5-HT(2B)R(−/−) cells rescued totally the alkaline phosphatase and osteopontin mRNA levels, cell-cell adhesion, and matrix mineralization. We conclude that the absence of 5-HT(2B) receptors leads to the overproduction of prostacyclin, inducing reduced osteoblast differentiation due to PPAR-ß/δ -dependent target regulation and defective cell-cell adhesion and matrix mineralization. This study thus reveals a previously unrecognized cell autonomous osteoblast defect in the absence of 5-HT(2B)R and highlights a new pathway linking 5-HT(2B) receptors and nuclear PPAR- ß/δ via prostacyclin.
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spelling pubmed-37757372013-09-25 Serotonin 2B Receptor (5-HT(2B) R) Signals through Prostacyclin and PPAR-ß/δ in Osteoblasts Chabbi-Achengli, Yasmine Launay, Jean-Marie Maroteaux, Luc de Vernejoul, Marie Christine Collet, Corinne PLoS One Research Article Osteoporosis is due to an imbalance between decreased bone formation by osteoblasts and increased resorption by osteoclasts. Deciphering factors controlling bone formation is therefore of utmost importance for the understanding and the treatment of osteoporosis. Our previous in vivo results showed that bone formation is reduced in the absence of the serotonin receptor 5-HT(2B), causing impaired osteoblast proliferation, recruitment, and matrix mineralization. In this study, we investigated the signaling pathways responsible for the osteoblast defect in 5-HT(2B)R(−/−) mice. Notably, we investigated the phospholipase A2 pathway and synthesis of eicosanoids in 5-HT(2B)R(−/−) compared to wild type (WT) osteoblasts. Compared to control osteoblasts, the lack of 5-HT(2B) receptors was only associated with a 10-fold over-production of prostacyclin (PGI(2)). Also, a specific prostacyclin synthase inhibitor (U51605) rescued totally osteoblast aggregation and matrix mineralization in the 5-HT(2B)R(−/−) osteoblasts without having any effect on WT osteoblasts. Prostacyclin is the endogenous ligand of the nuclear peroxisome proliferator activated receptor ß/δ (PPAR-ß/δ), and its inhibition in 5-HT(2B)R(−/−) cells rescued totally the alkaline phosphatase and osteopontin mRNA levels, cell-cell adhesion, and matrix mineralization. We conclude that the absence of 5-HT(2B) receptors leads to the overproduction of prostacyclin, inducing reduced osteoblast differentiation due to PPAR-ß/δ -dependent target regulation and defective cell-cell adhesion and matrix mineralization. This study thus reveals a previously unrecognized cell autonomous osteoblast defect in the absence of 5-HT(2B)R and highlights a new pathway linking 5-HT(2B) receptors and nuclear PPAR- ß/δ via prostacyclin. Public Library of Science 2013-09-17 /pmc/articles/PMC3775737/ /pubmed/24069449 http://dx.doi.org/10.1371/journal.pone.0075783 Text en © 2013 Chabbi-Achengli et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Chabbi-Achengli, Yasmine
Launay, Jean-Marie
Maroteaux, Luc
de Vernejoul, Marie Christine
Collet, Corinne
Serotonin 2B Receptor (5-HT(2B) R) Signals through Prostacyclin and PPAR-ß/δ in Osteoblasts
title Serotonin 2B Receptor (5-HT(2B) R) Signals through Prostacyclin and PPAR-ß/δ in Osteoblasts
title_full Serotonin 2B Receptor (5-HT(2B) R) Signals through Prostacyclin and PPAR-ß/δ in Osteoblasts
title_fullStr Serotonin 2B Receptor (5-HT(2B) R) Signals through Prostacyclin and PPAR-ß/δ in Osteoblasts
title_full_unstemmed Serotonin 2B Receptor (5-HT(2B) R) Signals through Prostacyclin and PPAR-ß/δ in Osteoblasts
title_short Serotonin 2B Receptor (5-HT(2B) R) Signals through Prostacyclin and PPAR-ß/δ in Osteoblasts
title_sort serotonin 2b receptor (5-ht(2b) r) signals through prostacyclin and ppar-ß/δ in osteoblasts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775737/
https://www.ncbi.nlm.nih.gov/pubmed/24069449
http://dx.doi.org/10.1371/journal.pone.0075783
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