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

Bing Shu, Yongjian Zhao, Yongjun Wang, Guangxi Wang, Xifu Shang, Michael Britt, Margaret Olmedo, Marjorie Chelly, Massimo Max Morandi, Shane Barton, Yufeng Dong

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13 Scopus citations

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.

Original languageEnglish (US)
Article number7002
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

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    Shu, B., Zhao, Y., Wang, Y., Wang, G., Shang, X., Britt, M., Olmedo, M., Chelly, M., Morandi, M. M., Barton, S., & Dong, Y. (2017). Oleanolic Acid Enhances Mesenchymal Stromal Cell Osteogenic Potential by Inhibition of Notch Signaling. Scientific Reports, 7(1), [7002]. https://doi.org/10.1038/s41598-017-07633-7