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Horm Metab Res 2016; 48(07): 468-475
DOI: 10.1055/s-0042-101027
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

In Vitro Effects of Pioglitazone on the Expression of Components of Wnt Signaling Pathway and Markers of Bone Mineralization

D. Avtanski
1   Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Breast Cancer Program, Johns Hopkins University, Baltimore, USA
,
Y. Hirth
2   Division of Endocrinology, Department of Medicine, Beth Israel Medical Center, Albert Einstein College of Medicine, The Friedman Diabetes Institute New York, New York, USA
,
N. Babushkin
2   Division of Endocrinology, Department of Medicine, Beth Israel Medical Center, Albert Einstein College of Medicine, The Friedman Diabetes Institute New York, New York, USA
,
V. Sy
2   Division of Endocrinology, Department of Medicine, Beth Israel Medical Center, Albert Einstein College of Medicine, The Friedman Diabetes Institute New York, New York, USA
,
D. Sharma
1   Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Breast Cancer Program, Johns Hopkins University, Baltimore, USA
,
L. Poretsky
2   Division of Endocrinology, Department of Medicine, Beth Israel Medical Center, Albert Einstein College of Medicine, The Friedman Diabetes Institute New York, New York, USA
3   Division of Endocrinology, Lenox Hill Hospital, Northwell Health New York, New York, USA
,
D. Seto-Young
2   Division of Endocrinology, Department of Medicine, Beth Israel Medical Center, Albert Einstein College of Medicine, The Friedman Diabetes Institute New York, New York, USA
› Author Affiliations
Further Information

Publication History

received 16 September 2015

accepted 07 January 2016

Publication Date:
05 February 2016 (online)

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Abstract

Pioglitazone is an insulin-sensitizing thiazolidinedione (TZD) whose use is associated with bone loss. We examined the effects of pioglitazone on components of the Wnt signaling pathway (Wnt1, β-catenin) and markers of bone mineralization [osteoprotegerin (OPG), bone sialoprotein (BSP), fibroblast growth factor (FGF)23] as well as mineral content in human osteoblast hFOB 1.19 cells. hFOB 1.19 cells were cultured in K12/DMD medium with or without pioglitazone. PPARγ Wnt1, OPG, BSP, or FGF23 mRNA expression was measured using qRT-PCR; β-catenin, OPG, BSP, or FGF23 using ELISA; and calcium or phosphate content using colorimetry. Treatment with pioglitazone resulted in increased expression of PPARγ mRNA in hFOB 1.19 osteoblasts. Pioglitazone decreased Wnt1 mRNA levels and suppressed components of Wnt signaling pathway as evidenced by a decrease in β-catenin gene expression and secretion as well as β-catenin specific activity. The expression and the activity of OPG, BSP, and FGF23 were also reduced by pioglitazone together with total (but not specific) calcium and phosphate content. Pioglitazone affects Wnt1 signaling pathway and mineral matrix regulation components in human osteoblasts.

Key words

PPARγ - β-catenin - BSP - OPG - FGF23 - calcium - phosphate
 

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