Oleanolic Acid Enhances Mesenchymal Stromal Cell Osteogenic Potential by Inhibition of Notch Signaling

Abstract Oleanolic acid (OA), a pentacyclic triterpenoid, has been shown to modulate multiple signaling pathways in a variety of cell linages. But the mechanisms underlying OA-mediated mesenchymal stromal cell (MSC) osteogenic differentiation are not known. In this study, we examined effects of OA o...

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Autores principales:	Bing Shu, Yongjian Zhao, Yongjun Wang, Guangxi Wang, Xifu Shang, Michael Britt, Margaret Olmedo, Marjorie Chelly, Massimo Max Morandi, Shane Barton, Yufeng Dong
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a3021b4744194ade8c2f5073b2a36a94
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spelling	oai:doaj.org-article:a3021b4744194ade8c2f5073b2a36a942021-12-02T16:06:57ZOleanolic Acid Enhances Mesenchymal Stromal Cell Osteogenic Potential by Inhibition of Notch Signaling10.1038/s41598-017-07633-72045-2322https://doaj.org/article/a3021b4744194ade8c2f5073b2a36a942017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07633-7https://doaj.org/toc/2045-2322Abstract Oleanolic acid (OA), a pentacyclic triterpenoid, has been shown to modulate multiple signaling pathways in a variety of cell linages. But the mechanisms underlying OA-mediated mesenchymal stromal cell (MSC) osteogenic differentiation are not known. In this study, we examined effects of OA on cell viability, osteogenic differentiation in MSCs, and the involvement of Notch and BMP signaling. OA induced bone marrow derived MSC differentiation towards osteoprogenitor cells and inhibited Notch signaling in a dose dependent manner. Constitutive activation of Notch signaling fully blocked OA induced MSC osteogenic differentiation. The expression level of early osteogenic marker genes, ALP, Runx2, and type I collagen, which play a critical role in MSC to osteoblast transition and servers as a downstream target of BMP signaling, was significantly induced by OA. Furthermore, BMP2 mediated MSC osteogenic differentiation was significantly enhance by OA treatment, indicating a synergistic effect between BMP2 and OA. Our results suggest that OA is a promising bioactive agent for bone tissue regeneration, and inhibition of Notch signaling is required for its osteogenic effects on MSCs.Bing ShuYongjian ZhaoYongjun WangGuangxi WangXifu ShangMichael BrittMargaret OlmedoMarjorie ChellyMassimo Max MorandiShane BartonYufeng DongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bing Shu Yongjian Zhao Yongjun Wang Guangxi Wang Xifu Shang Michael Britt Margaret Olmedo Marjorie Chelly Massimo Max Morandi Shane Barton Yufeng Dong Oleanolic Acid Enhances Mesenchymal Stromal Cell Osteogenic Potential by Inhibition of Notch Signaling
description	Abstract Oleanolic acid (OA), a pentacyclic triterpenoid, has been shown to modulate multiple signaling pathways in a variety of cell linages. But the mechanisms underlying OA-mediated mesenchymal stromal cell (MSC) osteogenic differentiation are not known. In this study, we examined effects of OA on cell viability, osteogenic differentiation in MSCs, and the involvement of Notch and BMP signaling. OA induced bone marrow derived MSC differentiation towards osteoprogenitor cells and inhibited Notch signaling in a dose dependent manner. Constitutive activation of Notch signaling fully blocked OA induced MSC osteogenic differentiation. The expression level of early osteogenic marker genes, ALP, Runx2, and type I collagen, which play a critical role in MSC to osteoblast transition and servers as a downstream target of BMP signaling, was significantly induced by OA. Furthermore, BMP2 mediated MSC osteogenic differentiation was significantly enhance by OA treatment, indicating a synergistic effect between BMP2 and OA. Our results suggest that OA is a promising bioactive agent for bone tissue regeneration, and inhibition of Notch signaling is required for its osteogenic effects on MSCs.
format	article
author	Bing Shu Yongjian Zhao Yongjun Wang Guangxi Wang Xifu Shang Michael Britt Margaret Olmedo Marjorie Chelly Massimo Max Morandi Shane Barton Yufeng Dong
author_facet	Bing Shu Yongjian Zhao Yongjun Wang Guangxi Wang Xifu Shang Michael Britt Margaret Olmedo Marjorie Chelly Massimo Max Morandi Shane Barton Yufeng Dong
author_sort	Bing Shu
title	Oleanolic Acid Enhances Mesenchymal Stromal Cell Osteogenic Potential by Inhibition of Notch Signaling
title_short	Oleanolic Acid Enhances Mesenchymal Stromal Cell Osteogenic Potential by Inhibition of Notch Signaling
title_full	Oleanolic Acid Enhances Mesenchymal Stromal Cell Osteogenic Potential by Inhibition of Notch Signaling
title_fullStr	Oleanolic Acid Enhances Mesenchymal Stromal Cell Osteogenic Potential by Inhibition of Notch Signaling
title_full_unstemmed	Oleanolic Acid Enhances Mesenchymal Stromal Cell Osteogenic Potential by Inhibition of Notch Signaling
title_sort	oleanolic acid enhances mesenchymal stromal cell osteogenic potential by inhibition of notch signaling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a3021b4744194ade8c2f5073b2a36a94
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Oleanolic Acid Enhances Mesenchymal Stromal Cell Osteogenic Potential by Inhibition of Notch Signaling

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