A novel semisynthetic molecule icaritin stimulates osteogenic differentiation and inhibits adipogenesis of mesenchymal stem cells.

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 (GSK3ß) and ß-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 GSK3ß 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 GSK3ß and PPARγ.

Iodine-131 induced hepatotoxicity in previously healthy patients with Grave's disease.

OBJECTIVE: To describe the association of the rare and serious complication of liver toxicity in previously healthy Grave's disease (GD) patients after the treatment with radioactive iodine (131)I (RAI). CASE PRESENTATION: We report the clinical, laboratory and pathologic findings of 2 cases of severe liver toxicity associated with the treatment with RAI in previously healthy patients with GD. Clinical examination and laboratory investigations excluded viral hepatitis, autoimmune hepatitis, granulomatous disease, primary biliary disease, extrahepatic biliary obstruction, and heart failure. Case 1: A previously healthy 52-years old man reportedly having a typical GD but following RAI treatment, concomitantly developed severe liver toxicity that required 1 week of treatment in hospital. Case 2: A previously healthy 34-years old woman is reported as having a typical GD but developed jaundice following RAI treatment that required several weeks of in hospital treatment in the hepato-biliary department. In both cases, the liver dysfunction resolved after intensive treatment with hepato-protective agents. In this report the therapeutic considerations as well as the pathogenetic possibilities are reviewed. CONCLUSION: To the best of our knowledge, this is the first description of the association observed, which is rare but may be severe and should be considered in any case of thyrotoxicosis where a liver dysfunction develops after the treatment with radioactive iodine (131)I.