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

• Published in: Scientific reports 2017-08, Vol.7 (1), p.7002-7002, Article 7002
• Main Authors: Shu, Bing, Zhao, Yongjian, Wang, Yongjun, Wang, Guangxi, Shang, Xifu, Britt, Michael, Olmedo, Margaret, Chelly, Marjorie, Morandi, Massimo Max, Barton, Shane, Dong, Yufeng
• Format: Article
• Language: English
• Subjects: 13; 13/1; 13/100; 13/109; 13/95; 631/80/86; 692/4017; 96; Acids; Bone growth; Bone marrow; Bone morphogenetic protein 2; Bone surgery; Cbfa-1 protein; Cell culture; Cell cycle; Cell Differentiation - drug effects; Cell Survival - drug effects; Cells, Cultured; Chinese medicine; Collagen (type I); Drug dosages; Fractures; Gene expression; Gene Expression Profiling; Humanities and Social Sciences; Humans; Mesenchymal Stem Cells - drug effects; Mesenchyme; multidisciplinary; Notch protein; Oleanolic acid; Oleanolic Acid - metabolism; Orthopedics; Osteogenesis - drug effects; Osteoprogenitor cells; Receptors, Notch - antagonists & inhibitors; Regeneration; Science; Science (multidisciplinary); Signal Transduction - drug effects; Stem cells; Synergistic effect
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-07633-7

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.