期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/ijms23020653
关键词
adipogenesis; AMPK; dracunculin; hBM-MSC; Wnt/beta-catenin
资金
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2020R1I1A3070750]
- Busan Metropolitan City and Busan Institute for Talent & Lifelong Education (BIT)
- National Research Foundation of Korea [2020R1I1A3070750] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
This study reported the anti-adipogenic effect of dracunculin (DCC) in human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). DCC inhibits lipid accumulation and the expression of adipogenic transcription factors. The mechanism of action involves activating the beta-catenin pathway via AMPK. DCC has potential use as a nutraceutical against bone marrow adiposity.
Increased bone marrow adiposity is widely observed in patients with obesity and osteoporosis and reported to have deleterious effects on bone formation. Dracunculin (DCC) is a coumarin isolated from Artemisia spp. but, until now, has not been studied for its bioactive potential except antitrypanosomal activity. In this context, current study has reported the anti-adipogenic effect of DCC in human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). DCC dose-dependently inhibited the lipid accumulation and expression of adipogenic transcription factors peroxisome proliferator-activated receptor gamma (PPAR gamma) and CCAAT/enhancer binding protein alpha (C/EBP alpha) in hBM-MSCs induced to undergo adipogenesis. To elucidate its action mechanism, the effect of DCC on Wnt/beta-catenin and AMPK pathways was examined. Results showed that DCC treatment activated Wnt/beta-catenin signaling pathway via AMPK evidenced by increased levels of AMPK phosphorylation and Wnt10b expression after DCC treatment. In addition, DCC treated adipo-induced hBM-MSCs exhibited significantly increased nuclear levels of beta-catenin compared with diminished nuclear PPAR gamma levels. In conclusion, DCC was shown to be able to hinder adipogenesis by activating the beta-catenin via AMPK, providing potential utilization of DCC as a nutraceutical against bone marrow adiposity.
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