International Journal of Medical Sciences

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21 October 2017

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Int J Med Sci 2013; 10(6):782-789. doi:10.7150/ijms.6084

Research Paper

A Novel Semisynthetic Molecule Icaritin Stimulates Osteogenic Differentiation and Inhibits Adipogenesis of Mesenchymal Stem Cells

Hui Sheng1,2,3*✉, Xue-fei Rui1,2*, Chun-Jun Sheng1, Wen-Jun Li1, Xiao-Yun Cheng1, Navina Priya Jhummon1, Yong-Chun Yu1, Shen Qu1, Ge Zhang4, Ling Qin4✉

1. Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China;
2. Department of Clinical Medicine, Nanjing Medical University, Nanjing, China;
3. Advanced Institute of Translational Medicine, Tongji University, Shanghai, China;
4. Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China.
* Co-first author

Abstract

Background We previously reported that the constitutional flavonoid glycosides derived from herb Epimedium (EF, composed of seven flavonoid compounds with common nuclear stem) exerted beneficial effects on the bone, including promoting bone formation and inhibiting bone marrow fat deposition. Recent in vivo study showed that Icaritin was a common metabolite of these constitutional flavonoid glycosides, indicating that Icaritin is a bioactive compound. The present study was designed to investigate whether Icaritin could promote osteogenic differentiation and suppress adipogenic differentiation of marrow mesenchymal stem cells (MSCs).

Methods Primary MSCs were harvested from adult mice and exposed to Icaritin to evaluate whether it could promote osteogenesis and suppress adipogenesis using the following assays: determination of alkaline phosphatase (ALP) activity and mineralization; mRNA expression of osteogenic differentiation marker Runx2; osteocalcin and bone sialoprotein (BSP) by RT-PCR; quantification of adipocyte-like cells by Oil Red O staining assay and mRNA expression for adipogenic differentiation markers peroxisome proliferator-activated receptor gamma (PPARγ); adipocyte fatty acid binding protein (aP2) and lipoprotein lipase (LPL) by RT-PCR. For the underlying mechanism, glycogen synthase kinase-3beta (GSK3β) and β-catenin were also explored by western blotting.

Results Icaritin promoted osteogenic differentiation and maturation of MSCs as indicated by increased mRNA expression for Runx2, osteocalcin and BSP, and enhanced ALP activity and mineralization; Icaritin inhibited adipogenic differentiation, as indicated by decreased mRNA expression for PPARγ, LPL, aP2, and suppressed formation of adipocyte-like cells; Icaritin inactivated GSK3β and suppressed PPARγ expression when promoting osteogenesis and suppressing adipogenesis of MSCs.

Conclusion This was the first study demonstrating that the novel semisynthetic molecule Icaritin could stimulate osteogenic differentiation and inhibit adipogenesis of MSCs, which was associated with the suppression of GSK3β and PPARγ.

Keywords: Mesenchymal stem cells, Icaritin, Adipogenesis, Osteogenesis, GSK3β, Osteoporosis.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Sheng H, Rui Xf, Sheng CJ, Li WJ, Cheng XY, Jhummon NP, Yu YC, Qu S, Zhang G, Qin L. A Novel Semisynthetic Molecule Icaritin Stimulates Osteogenic Differentiation and Inhibits Adipogenesis of Mesenchymal Stem Cells. Int J Med Sci 2013; 10(6):782-789. doi:10.7150/ijms.6084. Available from http://www.medsci.org/v10p0782.htm