Thiazolidinedione effects on the mineral content and the components of the Wnt signaling pathway in the human osteoblasts

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 199-233-Bone Biology
Basic/Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-214
Yael Hirth1, Nicole Babushkin1, Vanessa Sy1, Amit Kumar Seth1, Ashutosh S Pareek2, Yu Kuei Lin1, Leonid Poretsky2 and Donna L T Seto-Young*2
1Beth Israel Medical Center, New York, NY, 2Beth Israel Med Ctr, New York, NY
Introduction:Thiazolidinediones (TZDs, pioglitazone [P] and rosiglitazone [R]), are insulin sensitizers used for the treatment of diabetes. Multiple clinical trials demonstrated that TZDs increase the risk of fractures in postmenopausal women with type 2 diabetes.  Our recent studies demonstrated that TZDs induced mouse osteoblast adipogenesis, increased oleic acid uptake and inhibited alkaline phosphatase activity and osteocalcin synthesis.  In this report, we describe the TZD effects on bone sialoprotein (BSP) and fibroblast growth factor-23 (FGF-23) synthesis, as well as mineral content of calcium and phosphate accumulation. Additionally, we examined the synthesis of Wnt signaling pathway components (namely β-catanin, osteoprotegerin [OPG] and receptor activator of nuclear factor kappa -β ligand [RANKL]).

Materials & Methods: Human osteoblasts (hFOB 1.19) were cultured and incubated in a medium with or without pioglitazone or rosiglitazone (5-20 μM). BSP, β-catanin, OPG, RANKL, FGF-23 (ELISA) and calcium and phosphate concentrations (colorimetric method) were measured.

Results: P and R inhibited BSP synthesis by 29.5% (p<0.028) and 26.6% (p<0.001), respectively. Calcium content was inhibited by 29.9% (p<0.001) and 23.1% and phosphate content was inhibited by 23.0% (p<0.001) and 29.6% (p<0.001), respectively by P and R. FGF-23 production was not significantly changed. However, at a concentration of 20 μM, P and R enhanced the FGF-23 production by 39% (p<0.047) and 109% (p<0.033), respectively.  β-catanin was inhibited by P and R by 71.3% (p<0.001) and 50.8% (p<0.006) and OPG synthesis was inhibited by 70% (p<0.001) and 55.8% (p<0.001), respectively. Total RANKL production was not significantly affected. 

Conclusion: TZDs inhibit BSP, β-catanin and OPG production, as well as calcium and phosphate content in cultured human osteoblasts.  High concentration of TZDs (20 μM) enhances FGF-23 production.  RANKL synthesis is not affected by TZDs. Thus, TZDs not only induce adipogenesis, but also affect the mineral content and the components of the Wnt signaling pathway in human osteoblasts.

Nothing to Disclose: YH, NB, VS, AKS, ASP, YKL, LP, DLTS

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This work was supported in part by Gerald J. and Dorothy Friedman New York Foundation for Medical Research, by the Empire Clinical Research Investigator Program of the New York State Department of Health, by the Chinese American Medical Society & Chinese American Independent Practice Association and by Yen Family Foundation.