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

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.

Icariin prevents ovariectomy-induced bone loss and lowers marrow adipogenesis

“…Previous ex vivo studies have revealed that, in addition to having inhibitory effects on osteoclast proliferation, maturation, and differentiation, estrogens can inhibit adipocyte differentiation and function via down-regulation of the expression of adipogenesis-related genes. In a recent study, Sheng et al 18 investigated the effect of ICA on mice MSCs induced to differentiate into either osteoblasts or adipocytes. 42<44 Other osteoporosis treatments have been shown to inhibit marrow adipogenesis in vivo; for example, risedronate and peroxisome proliferator-activated receptor-F 2 antagonist (bisphenol-A-diglycidyl ether) have been shown to lower marrow adipose tissue volume in both human and animal models.…”

Icariin-Loaded TiO2 Nanotubes for Regulation of the Bioactivity of Bone Marrow Cells

“…Icariin (ICA, C 33 H 40 O 15 ; molecular weight: 676.67) is the major flavonoid glycoside extracted from Epimedium and is considered the main active constituent. ICA may exert favorable osseointegration effects by enhancing the differentiation of MSCs into osteoblasts while inhibiting the adipogenesis of bone marrow cells [17] and can treat osteoporosis by increasing bone mineral content [18]. Recently, ICA has been widely applied for bone tissue engineering due to its safe, nontoxic, and osteoinductive properties as well as its low cost [19,20].…”

Icaritin suppresses the proliferation of human osteosarcoma cells in vitro by increasing apoptosis and decreasing MMP expression

“…Icaritin, a prenylflavonoid derivative from the Chinese tonic herb Epimedium, has been shown to have many pharmacological and biological activities, such as antioxidant activity [1] , enhancement of the osteoblastic differentiation of mesenchymal stem cells [2][3][4] , inhibition of human prostate carcinoma growth [5,6] and neuroprotective effects [7][8][9] .…”