Prostaglandin E2 inhibits matrix mineralization by human bone marrow stromal cell-derived osteoblasts via Epac-dependent cAMP signaling

Abstract The osteoinductive properties of prostaglandin E2 (PGE2) and its signaling pathways have led to suggestions that it may serve as a potential therapeutic strategy for bone loss. However, the prominence of PGE2 as an inducer of bone formation is attributed primarily to findings from studies u...

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Autores principales:	Ali Mirsaidi, André N. Tiaden, Peter J. Richards
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5f25069ab83e421e930f6316dbda8d52
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spelling	oai:doaj.org-article:5f25069ab83e421e930f6316dbda8d522021-12-02T12:32:44ZProstaglandin E2 inhibits matrix mineralization by human bone marrow stromal cell-derived osteoblasts via Epac-dependent cAMP signaling10.1038/s41598-017-02650-y2045-2322https://doaj.org/article/5f25069ab83e421e930f6316dbda8d522017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02650-yhttps://doaj.org/toc/2045-2322Abstract The osteoinductive properties of prostaglandin E2 (PGE2) and its signaling pathways have led to suggestions that it may serve as a potential therapeutic strategy for bone loss. However, the prominence of PGE2 as an inducer of bone formation is attributed primarily to findings from studies using rodent models. In the current study, we investigated the effects of PGE2 on human bone marrow stromal cell (hBMSC) lineage commitment and determined its mode of action. We demonstrated that PGE2 treatment of hBMSCs significantly altered the expression profile of several genes associated with osteoblast differentiation (RUNX2 and ALP) and maturation (BGLAP and MGP). This was attributed to the activation of specific PGE2 receptors, and was associated with increases in cAMP production and sustained AKT phosphorylation. Pharmacological inhibition of exchange protein directly activated by cAMP (Epac), but not protein kinase A (PKA), recovered the mineralization functions of hBMSC-derived osteoblasts treated with PGE2 and restored AKT phosphorylation, along with the expression levels of RUNX2, ALP, BGLAP and MGP. Our findings therefore provide insights into how PGE2 influences hBMSC-mediated matrix mineralization, and should be taken into account when evaluating the role of PGE2 in human bone metabolism.Ali MirsaidiAndré N. TiadenPeter J. RichardsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ali Mirsaidi André N. Tiaden Peter J. Richards Prostaglandin E2 inhibits matrix mineralization by human bone marrow stromal cell-derived osteoblasts via Epac-dependent cAMP signaling
description	Abstract The osteoinductive properties of prostaglandin E2 (PGE2) and its signaling pathways have led to suggestions that it may serve as a potential therapeutic strategy for bone loss. However, the prominence of PGE2 as an inducer of bone formation is attributed primarily to findings from studies using rodent models. In the current study, we investigated the effects of PGE2 on human bone marrow stromal cell (hBMSC) lineage commitment and determined its mode of action. We demonstrated that PGE2 treatment of hBMSCs significantly altered the expression profile of several genes associated with osteoblast differentiation (RUNX2 and ALP) and maturation (BGLAP and MGP). This was attributed to the activation of specific PGE2 receptors, and was associated with increases in cAMP production and sustained AKT phosphorylation. Pharmacological inhibition of exchange protein directly activated by cAMP (Epac), but not protein kinase A (PKA), recovered the mineralization functions of hBMSC-derived osteoblasts treated with PGE2 and restored AKT phosphorylation, along with the expression levels of RUNX2, ALP, BGLAP and MGP. Our findings therefore provide insights into how PGE2 influences hBMSC-mediated matrix mineralization, and should be taken into account when evaluating the role of PGE2 in human bone metabolism.
format	article
author	Ali Mirsaidi André N. Tiaden Peter J. Richards
author_facet	Ali Mirsaidi André N. Tiaden Peter J. Richards
author_sort	Ali Mirsaidi
title	Prostaglandin E2 inhibits matrix mineralization by human bone marrow stromal cell-derived osteoblasts via Epac-dependent cAMP signaling
title_short	Prostaglandin E2 inhibits matrix mineralization by human bone marrow stromal cell-derived osteoblasts via Epac-dependent cAMP signaling
title_full	Prostaglandin E2 inhibits matrix mineralization by human bone marrow stromal cell-derived osteoblasts via Epac-dependent cAMP signaling
title_fullStr	Prostaglandin E2 inhibits matrix mineralization by human bone marrow stromal cell-derived osteoblasts via Epac-dependent cAMP signaling
title_full_unstemmed	Prostaglandin E2 inhibits matrix mineralization by human bone marrow stromal cell-derived osteoblasts via Epac-dependent cAMP signaling
title_sort	prostaglandin e2 inhibits matrix mineralization by human bone marrow stromal cell-derived osteoblasts via epac-dependent camp signaling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5f25069ab83e421e930f6316dbda8d52
work_keys_str_mv	AT alimirsaidi prostaglandine2inhibitsmatrixmineralizationbyhumanbonemarrowstromalcellderivedosteoblastsviaepacdependentcampsignaling AT andrentiaden prostaglandine2inhibitsmatrixmineralizationbyhumanbonemarrowstromalcellderivedosteoblastsviaepacdependentcampsignaling AT peterjrichards prostaglandine2inhibitsmatrixmineralizationbyhumanbonemarrowstromalcellderivedosteoblastsviaepacdependentcampsignaling
_version_	1718393980621684736

Prostaglandin E2 inhibits matrix mineralization by human bone marrow stromal cell-derived osteoblasts via Epac-dependent cAMP signaling

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