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

被引:4
作者
Avtanski, D. [1 ]
Hirth, Y. [2 ]
Babushkin, N. [2 ]
Sy, V. [2 ]
Sharma, D. [1 ]
Poretsky, L. [2 ,3 ]
Seto-Young, D. [2 ]
机构
[1] Johns Hopkins Univ, Breast Canc Program, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD USA
[2] Albert Einstein Coll Med, Friedman Diabet Inst, Beth Israel Med Ctr, Div Endocrinol,Dept Med, New York, NY USA
[3] Lenox Hill Hosp, Northwell Hlth, Div Endocrinol, New York, NY USA
关键词
PPAR gamma; beta-catenin; BSP; OPG; FGF23; calcium; phosphate; GROWTH-FACTOR; 23; PPAR-GAMMA; OSTEOPROTEGERIN; ROSIGLITAZONE; SERUM; THIAZOLIDINEDIONES; SIALOPROTEIN; BIOMARKERS; DENSITY; LIGAND;
D O I
10.1055/s-0042-101027
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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, beta-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. PPAR gamma Wnt1, OPG, BSP, or FGF23 mRNA expression was measured using qRT-PCR; beta-catenin, OPG, BSP, or FGF23 using ELISA; and calcium or phosphate content using colorimetry. Treatment with pioglitazone resulted in increased expression of PPAR gamma mRNA in hFOB 1.19 osteoblasts. Pioglitazone decreased Wnt1 mRNA levels and suppressed components of Wnt signaling pathway as evidenced by a decrease in beta-catenin gene expression and secretion as well as beta-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.
引用
收藏
页码:468 / 475
页数:8
相关论文
共 48 条
[1]   Osteoprotegerin: Multiple partners for multiple functions [J].
Baud'huin, Marc ;
Duplomb, Laurence ;
Teletchea, Stephane ;
Lamoureux, Francois ;
Ruiz-Velasco, Carmen ;
Maillasson, Mike ;
Redini, Francoise ;
Heymann, Marie-Francoise ;
Heymann, Dominique .
CYTOKINE & GROWTH FACTOR REVIEWS, 2013, 24 (05) :401-409
[2]   Rosiglitazone decreases serum bone-specific alkaline phosphatase activity in postmenopausal diabetic women [J].
Berberoglu, Zehra ;
Gursoy, Alptekin ;
Bayraktar, Nilufer ;
Yazici, Ayse Canan ;
Tutuncu, Neslihan Bascil ;
Demirag, Nilgun Guvener .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2007, 92 (09) :3523-3530
[3]   Effects of rosiglitazone on bone mineral density and remodelling parameters in Postmenopausal diabetic women: a 2-year follow-up study [J].
Berberoglu, Zehra ;
Yazici, Ayse C. ;
Demirag, Nilgun G. .
CLINICAL ENDOCRINOLOGY, 2010, 73 (03) :305-312
[4]   Thiazolidinediones: Pleiotropic drugs with potent anti-inflammatory properties for tissue protection [J].
Buckingham, RE .
HEPATOLOGY RESEARCH, 2005, 33 (02) :167-170
[5]   Wnt signalling in pituitary development and tumorigenesis [J].
Chambers, T. J. G. ;
Giles, A. ;
Brabant, G. ;
Davis, J. R. E. .
ENDOCRINE-RELATED CANCER, 2013, 20 (03) :R101-R111
[6]   Wnt/β-Catenin Signaling and Disease [J].
Clevers, Hans ;
Nusse, Roel .
CELL, 2012, 149 (06) :1192-1205
[7]   RANKL/OPG Ratio and DKK-1 Expression in Primary Osteoblastic Cultures from Osteoarthritic and Osteoporotic Subjects [J].
Corrado, Addolorata ;
Neve, Anna ;
Macchiarola, Antonio ;
Gaudio, Annamaria ;
Marucci, Arcangela ;
Cantatore, Francesco Paolo .
JOURNAL OF RHEUMATOLOGY, 2013, 40 (05) :684-694
[8]   High fatty acid content in rabbit serum is responsible for the differentiation of osteoblasts into adipocyte-like cells [J].
Diascro, DD ;
Vogel, RL ;
Johnson, TE ;
Witherup, KM ;
Pitzenberger, SM ;
Rutledge, SJ ;
Prescott, DJ ;
Rodan, GA ;
Schmidt, A .
JOURNAL OF BONE AND MINERAL RESEARCH, 1998, 13 (01) :96-106
[9]   The role of Fibroblast Growth Factor 23 in chronic kidney disease-mineral and bone disorder [J].
Diniz, Hugo ;
Frazao, Joao M. .
NEFROLOGIA, 2013, 33 (06) :835-844
[10]   A SENSITIVE, HIGH-VOLUME, COLORIMETRIC ASSAY FOR PROTEIN PHOSPHATASES [J].
FISHER, DK ;
HIGGINS, TJ .
PHARMACEUTICAL RESEARCH, 1994, 11 (05) :759-763