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Sci Rep. 2017 Aug 1;7(1):7002. doi: 10.1038/s41598-017-07633-7.

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

Author information

1
Longhua Hospital and Key Laboratory of Ministry of Education of China, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
2
Department of Orthopedic Surgery, LSU Health Sciences Center, Shreveport, LA, USA.
3
Department of Orthopedic Surgery, Anhui Provincial Hospital, Hefei, Anhui, China.
4
Longhua Hospital and Key Laboratory of Ministry of Education of China, Shanghai University of Traditional Chinese Medicine, Shanghai, China. ydong@lsuhsc.edu.
5
Department of Orthopedic Surgery, LSU Health Sciences Center, Shreveport, LA, USA. ydong@lsuhsc.edu.

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.

PMID:
28765584
PMCID:
PMC5539294
DOI:
10.1038/s41598-017-07633-7
[Indexed for MEDLINE]
Free PMC Article

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