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Sphingosine-1-Phosphate Receptor 2 Controls Podosome Components Induced by RANKL Affecting Osteoclastogenesis and Bone Resorption
Proinflammatory cytokine production, cell chemotaxis, and osteoclastogenesis can lead to inflammatory bone loss. Previously, we showed that sphingosine-1-phosphate receptor 2 (S1PR2), a G protein coupled receptor, regulates inflammatory cytokine production and osteoclastogenesis. However, the signal...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357083/ https://www.ncbi.nlm.nih.gov/pubmed/30609675 http://dx.doi.org/10.3390/cells8010017 |
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author | Hsu, Li-Chien Reddy, Sakamuri V. Yilmaz, Özlem Yu, Hong |
author_facet | Hsu, Li-Chien Reddy, Sakamuri V. Yilmaz, Özlem Yu, Hong |
author_sort | Hsu, Li-Chien |
collection | PubMed |
description | Proinflammatory cytokine production, cell chemotaxis, and osteoclastogenesis can lead to inflammatory bone loss. Previously, we showed that sphingosine-1-phosphate receptor 2 (S1PR2), a G protein coupled receptor, regulates inflammatory cytokine production and osteoclastogenesis. However, the signaling pathways regulated by S1PR2 in modulating inflammatory bone loss have not been elucidated. Herein, we demonstrated that inhibition of S1PR2 by a specific S1PR2 antagonist (JTE013) suppressed phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinases (MAPKs), and nuclear factor kappa-B (NF-κB) induced by an oral bacterial pathogen, Aggregatibacter actinomycetemcomitans, and inhibited the release of IL-1β, IL-6, TNF-α, and S1P in murine bone marrow cells. In addition, shRNA knockdown of S1PR2 or treatment by JTE013 suppressed cell chemotaxis induced by bacteria-stimulated cell culture media. Furthermore, JTE013 suppressed osteoclastogenesis and bone resorption induced by RANKL in murine bone marrow cultures. ShRNA knockdown of S1PR2 or inhibition of S1PR2 by JTE013 suppressed podosome components, including PI3K, Src, Pyk2, integrin β(3,) filamentous actin (F-actin), and paxillin levels induced by RANKL in murine bone marrow cells. We conclude that S1PR2 plays an essential role in modulating proinflammatory cytokine production, cell chemotaxis, osteoclastogenesis, and bone resorption. Inhibition of S1PR2 signaling could be a novel therapeutic strategy for bone loss associated with skeletal diseases. |
format | Online Article Text |
id | pubmed-6357083 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63570832019-02-06 Sphingosine-1-Phosphate Receptor 2 Controls Podosome Components Induced by RANKL Affecting Osteoclastogenesis and Bone Resorption Hsu, Li-Chien Reddy, Sakamuri V. Yilmaz, Özlem Yu, Hong Cells Article Proinflammatory cytokine production, cell chemotaxis, and osteoclastogenesis can lead to inflammatory bone loss. Previously, we showed that sphingosine-1-phosphate receptor 2 (S1PR2), a G protein coupled receptor, regulates inflammatory cytokine production and osteoclastogenesis. However, the signaling pathways regulated by S1PR2 in modulating inflammatory bone loss have not been elucidated. Herein, we demonstrated that inhibition of S1PR2 by a specific S1PR2 antagonist (JTE013) suppressed phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinases (MAPKs), and nuclear factor kappa-B (NF-κB) induced by an oral bacterial pathogen, Aggregatibacter actinomycetemcomitans, and inhibited the release of IL-1β, IL-6, TNF-α, and S1P in murine bone marrow cells. In addition, shRNA knockdown of S1PR2 or treatment by JTE013 suppressed cell chemotaxis induced by bacteria-stimulated cell culture media. Furthermore, JTE013 suppressed osteoclastogenesis and bone resorption induced by RANKL in murine bone marrow cultures. ShRNA knockdown of S1PR2 or inhibition of S1PR2 by JTE013 suppressed podosome components, including PI3K, Src, Pyk2, integrin β(3,) filamentous actin (F-actin), and paxillin levels induced by RANKL in murine bone marrow cells. We conclude that S1PR2 plays an essential role in modulating proinflammatory cytokine production, cell chemotaxis, osteoclastogenesis, and bone resorption. Inhibition of S1PR2 signaling could be a novel therapeutic strategy for bone loss associated with skeletal diseases. MDPI 2019-01-01 /pmc/articles/PMC6357083/ /pubmed/30609675 http://dx.doi.org/10.3390/cells8010017 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hsu, Li-Chien Reddy, Sakamuri V. Yilmaz, Özlem Yu, Hong Sphingosine-1-Phosphate Receptor 2 Controls Podosome Components Induced by RANKL Affecting Osteoclastogenesis and Bone Resorption |
title | Sphingosine-1-Phosphate Receptor 2 Controls Podosome Components Induced by RANKL Affecting Osteoclastogenesis and Bone Resorption |
title_full | Sphingosine-1-Phosphate Receptor 2 Controls Podosome Components Induced by RANKL Affecting Osteoclastogenesis and Bone Resorption |
title_fullStr | Sphingosine-1-Phosphate Receptor 2 Controls Podosome Components Induced by RANKL Affecting Osteoclastogenesis and Bone Resorption |
title_full_unstemmed | Sphingosine-1-Phosphate Receptor 2 Controls Podosome Components Induced by RANKL Affecting Osteoclastogenesis and Bone Resorption |
title_short | Sphingosine-1-Phosphate Receptor 2 Controls Podosome Components Induced by RANKL Affecting Osteoclastogenesis and Bone Resorption |
title_sort | sphingosine-1-phosphate receptor 2 controls podosome components induced by rankl affecting osteoclastogenesis and bone resorption |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357083/ https://www.ncbi.nlm.nih.gov/pubmed/30609675 http://dx.doi.org/10.3390/cells8010017 |
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