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Pioglitazone AND bone

Morten A Karsdal, Kim Henriksen, Federica Genovese, Diana J Leeming, Mette J Nielsen, Bente J Riis, Claus Christiansen, Inger Byrjalsen, Detlef Schuppan
AIMS/HYPOTHESIS: The treatment of type 2 diabetes with full peroxisome proliferator-activated receptor gamma (PPARγ) agonists improves insulin sensitivity, but is associated with weight gain, heart failure, peripheral oedema and bone loss. Endotrophin, the C-terminal fragment of the α3 chain of procollagen type VI (also called Pro-C6), is involved in both adipose tissue matrix remodelling and metabolic control. We established a serum assay for endotrophin to assess if this novel adipokine could identify type 2 diabetic patients who respond optimally to PPARγ agonists, improving the risk-to-benefit ratio...
September 8, 2016: Diabetologia
Sara E Espinoza, Chen-Pin Wang, Devjit Tripathy, Stephen C Clement, Dawn C Schwenke, Mary Ann Banerji, George A Bray, Thomas A Buchanan, Robert R Henry, Abbas E Kitabchi, Sunder Mudaliar, Frankie B Stentz, Peter D Reaven, Ralph A DeFronzo, Nicolas Musi
To determine the efficacy of pioglitazone to prevent type 2 diabetes in older compared to younger adults with pre-diabetes. Six hundred two participants with impaired glucose tolerance (IGT) were randomized in double blind fashion to placebo or pioglitazone for diabetes prevention in the ACT NOW study (NEJM 364:1104-1115, 2011). Cox proportional hazard regression was used to compare time to development of diabetes over a mean of 2 years between older (≥61 years) and younger participants. We compared effects of pioglitazone versus placebo on metabolic profiles, inflammatory markers, adipokines, β cell function (disposition index), insulin sensitivity (Matsuda index), and body composition by ANOVA...
September 1, 2016: Age (2005-)
Fei Xu, Yonghui Dong, Xin Huang, Peng Chen, Fengjing Guo, Anmin Chen, Shilong Huang
Thiazolidinediones are traditional anti‑diabetic therapeutic agents that have been associated with bone loss and increased fracture risk. However, the underlying mechanisms of this side effect require further elucidation. The present study aimed to investigate the effect of pioglitazone (PIO), a thiazolidinedione, on osteoblastogenesis, osteoclastogenesis and the osteoprotegerin (OPG) / receptor activator of nuclear factor‑κB ligand (RANKL) / RANK system. The MC3T3‑E1 murine pre‑osteoblastic cell line was treated with PIO and processed for reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis of OPG, RANKL, peroxisome proliferator‑activated receptor γ (PPARγ), Runt‑related transcription factor 2 (RUNX2), alkaline phosphatase (ALP) and osteocalcin (OCN), and western blotting analysis of OPG and RANKL...
September 2016: Molecular Medicine Reports
Philip M Bath, Jason P Appleton, Nikola Sprigg
The prevention of recurrent events after ischaemic stroke and transient ischaemic attack is well established and based on lifestyle changes, antithrombotics, statins, antihypertensives and carotid surgery. The international IRIS trial assessed whether pioglitazone, a glucose-lowering insulin-sensitizing drug, would reduce recurrent vascular events in patients with ischaemic stroke or transient ischaemic attack. After 4.8 years, pioglitazone therapy was associated with reduced vascular events and new diabetes, and an increase in weight, oedema and bone fractures...
October 2016: International Journal of Stroke: Official Journal of the International Stroke Society
Xian Jin, Liang Liu, Zhong'e Zhou, Junhua Ge, Tongqing Yao, Chengxing Shen
Classically activated macrophages (M1) are associated with inflammation in diabetic patients. Inflammation is a known risk factor in diabetes. The present study tested the hypothesis that pioglitazone (PIO) alleviates inflammation in diabetic mice fed a high-fat diet by inhibiting advanced glycation end-product (AGE)-induced classical macrophage activation. It was found that AGE treatment promoted the transcription of pro-inflammatory molecules and M1 surface markers, whereas PIO increased the expression of anti-inflammatory genes and decreased the expression of pro-inflammatory mediators in bone marrow-derived macrophages (BMDMs) in a dose-dependent manner...
June 2016: FEBS Journal
Boon-Yin Khoo, Kalpanah Nadarajan, Siang-Yian Shim, Noorizan Miswan, Chuan-Bing Zang, Kurt Possinger, Elena Elstner
The present study aimed to investigate the effects of bone marrow‑derived mesenchymal stem cells (BMSCs) that had been pretreated with pioglitazone and/or rosiglitazone on the growth and proliferation rate of MCF‑7 cells. The adhesive interaction between the BMSCs and the MCF‑7 cancer cells revealed that the pretreatment of BMSCs with a combination of two types of thiazolidinedione drug reduced the growth and proliferation rate of the MCF‑7 cells. The proliferation rate of the MCF‑7 cells could also be reduced by the non‑adhesive interaction of the cancer cells with BMSCs pretreated with pioglitazone and/or rosiglitazone...
April 2016: Molecular Medicine Reports
H Z Liu, Q Y Wang, Y Zhang, D T Qi, M W Li, W Q Guo, Y H Ma, L Y Wang, Y Chen, C Y Gao
Long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) is expressed in endothelial cells and involved in angiogenesis and vascular function. It was proposed that MEG3 participates in the process of endothelial progenitor cells (EPCs) functions in metabolic syndrome (MetS). In this study, the circulating EPCs number and function were decreased in MetS subjects. The MEG3 expression was expressed at a lower level and microRNA-140-5p (miR-140-5p) was expressed at a higher level in circulating EPCs of subjects with MetS...
March 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Walter N Kernan, Catherine M Viscoli, Karen L Furie, Lawrence H Young, Silvio E Inzucchi, Mark Gorman, Peter D Guarino, Anne M Lovejoy, Peter N Peduzzi, Robin Conwit, Lawrence M Brass, Gregory G Schwartz, Harold P Adams, Leo Berger, Antonio Carolei, Wayne Clark, Bruce Coull, Gary A Ford, Dawn Kleindorfer, John R O'Leary, Mark W Parsons, Peter Ringleb, Souvik Sen, J David Spence, David Tanne, David Wang, Toni R Winder
BACKGROUND: Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. METHODS: In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo...
April 7, 2016: New England Journal of Medicine
M van de Vyver, C Niesler, K H Myburgh, W F Ferris
Metabolic dysfunction that occurs in obesity and Type 2 diabetes results in a low-level inflammatory state which impacts on mesenchymal stem cells (MSCs) capacity to promote wound healing. The ability of either recombinant Interleukin-6 (rIL6) or pioglitazone to modulate MSC migration, essential for wound healing, by targeting the inflammation-modulated IL6/STAT3 signalling pathway was therefore investigated in bone marrow-derived MSCs from control (C57BL/6J) and pre-diabetic obese mice (B6. Cg-Lepob/J). The population doubling time, in vitro wound closure and mRNA expression profile of 84 genes involved in the IL6/STAT3 signalling pathway were assessed...
May 5, 2016: Molecular and Cellular Endocrinology
D Avtanski, Y Hirth, N Babushkin, V Sy, D Sharma, L Poretsky, D Seto-Young
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...
July 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Massoud Vosough, Shirin Moossavi, Soura Mardpour, Shahram Akhlaghpoor, Vajiheh Azimian, Neda Jarughi, Seyedeh-Esmat Hosseini, Mandana Ashrafi, Sepideh Nikfam, Nasser Aghdami, Reza Malekzadeh, Mehdi Mohamadnejad, Hossein Baharvand
BACKGROUND: Transplantation of mesenchymal stem cells (MSCs) in combination with pioglitazone, an agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ), can reduce liver fibrosis in models of liver injury. In this study, we conducted a pilot study of intraportal infusion of autologous MSCs in combination with pioglitazone to assess safety, feasibility, and effectiveness in patients with compensated cirrhosis. METHODS: Two patients with compensated cirrhosis were enrolled in this study...
February 2016: Archives of Iranian Medicine
Soichi Nakashiro, Tetsuya Matoba, Ryuta Umezu, Jun-Ichiro Koga, Masaki Tokutome, Shunsuke Katsuki, Kaku Nakano, Kenji Sunagawa, Kensuke Egashira
OBJECTIVE: Inflammatory monocytes/macrophages produce various proteinases, including matrix metalloproteinases, and degradation of the extracellular matrix by these activated proteinases weakens the mechanical strength of atherosclerotic plaques, which results in a rupture of the plaque. Peroxisome proliferator-activated receptor-γ induces a polarity shift of monocytes/macrophages toward less inflammatory phenotypes and has the potential to prevent atherosclerotic plaque ruptures. Therefore, we hypothesized that nanoparticle-mediated targeted delivery of the peroxisome proliferator-activated receptor-γ agonist pioglitazone into circulating monocytes could effectively inhibit plaque ruptures in a mouse model...
March 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Jing Wu, Nan Ru, Song Li
PURPOSE: The effectiveness of rapid maxillary expansion is adversely affected by failure and relapse. It is important to identify key factors that increase new bone formation and improve bone remodeling of midpalatal sutures to improve the stability and effectiveness of this commonly used orthodontic procedure. Peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in modulating osteogenesis and bone resorption in long bones. This study was designed to explore the function of PPARγ in bone remodeling and tissue engineering of midpalatal sutures...
November 2015: International Journal of Oral & Maxillofacial Implants
Ann V Schwartz, Haiying Chen, Walter T Ambrosius, Ajay Sood, Robert G Josse, Denise E Bonds, Adrian M Schnall, Eric Vittinghoff, Douglas C Bauer, Mary Ann Banerji, Robert M Cohen, Bruce P Hamilton, Tamara Isakova, Deborah E Sellmeyer, Debra L Simmons, Amal Shibli-Rahhal, Jeff D Williamson, Karen L Margolis
CONTEXT: In trials, thiazolidinediones (TZDs) increase fracture risk in women, but the effects of discontinuation are unknown. OBJECTIVE: The objective was to investigate the effects of TZD use and discontinuation on fractures in women and men. DESIGN: This was a longitudinal observational cohort study using data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial bone ancillary study. Duration of TZD use and discontinuation during ACCORD, assessed every 2-4 months at clinic visits, were modeled as time-varying covariates in proportional hazards models for occurrence of first non-spine fracture...
November 2015: Journal of Clinical Endocrinology and Metabolism
Renyuan Li, Wen Xu, Sihui Luo, Haixia Xu, Guoyu Tong, Longyi Zeng, Dalong Zhu, Jianping Weng
AIM: Preclinical studies suggested that insulin, incretin and thiazolidinediones had effect on regulation of bone metabolism. But clinical evidence is limited. We assessed the effects of these antihyperglycemic agents on bone metabolism in patients with newly diagnosed type 2 diabetes. METHODS: The present study was a two-center, randomized, parallel-group clinical trial. Sixty-two newly diagnosed and drug-naïve patients with type 2 diabetes were randomized to exenatide (EXE, n = 20), mixed protamine zinc recombinant human insulin lispro injection (25R; INS, n = 21) or pioglitazone (PIO, n = 21) group for a 24-week treatment...
December 2015: Acta Diabetologica
Nassera Aouali, Angeliki Broukou, Manon Bosseler, Olivier Keunen, Vincent Schlesser, Bassam Janji, Valerie Palissot, Philippe Stordeur, Guy Berchem
Epigenetic modifications play a major role in the development of multiple myeloma. We have previously reported that the PPARγ agonist pioglitazone (PIO) enhances, in-vitro, the cytotoxic effect of the Histone deacetylase inhibitor (HDACi), valproic acid (VPA), on multiple myeloma cells. Here, we described the development of a new multiple myeloma mouse model using MOLP8 cells, in order to evaluate the effect of VPA/PIO combination on the progression of myeloma cells, by analyzing the proliferation of bone marrow plasma cells...
2015: PloS One
Miao Duan, Bowen Zhou, Xinrong Zhou, Gang Yuan
BACKGROUND: Peroxisome proliferator-activated receptor γ (PPARγ) and Wnt play different roles in bone homeostasis. Thiazolidinediones are PPARγ agonists that cause bone mineral density loss. This study investigated the relationship between PPARγ and Wnt/β-catenin signaling in mouse osteoblastic MC3T3-E1 cells. METHODS: MC3T3-E1 cells were treated with either pioglitazone (Pio) or rosiglitazone (Rosi), thiazolidinediones, for 24 hours at 10 to 40-μM concentrations...
June 2015: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
Susan Y Smith, Rana Samadfam, Luc Chouinard, Malaika Awori, Agnes Bénardeau, Frieder Bauss, Robert E Guldberg, Elena Sebokova, Matthew B Wright
Pioglitazone, the peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist is an effective therapy for type 2 diabetes, but has been associated with increased risk for bone fracture. Preclinical studies suggest that PPAR-α agonists (e.g., fenofibrate) increase bone mineral density/content, although clinical data on bone effects of fibrates are lacking. We investigated the effects of pioglitazone (10 mg/kg/day) and fenofibrate (25 mg/kg/day) on bone strength and bone histomorphometric parameters in osteopenic ovariectomized (OVX) rats...
November 2015: Journal of Bone and Mineral Metabolism
Anil Bhansali, Vimal Upreti, Rama Walia, Vivek Gupta, Shobhit Bhansali, R R Sharma, Sandeep Grover, Neelam Marwaha, Niranjan Khandelwal
BACKGROUND: there are dearths of studies describing the effect of autologous bone marrow derived stem cell transplantation (ABMSCT) through targeted approach in Type 2 Diabetes Mellitus. This study reports the efficacy and safety of super-selective injection of ABMSCT in T2DM. MATERIALS AND METHODS: Ten patients (8 men and 2 women) with T2DM, with duration of disease >5 years and with documented triple drug failure receiving insulin (0.7 U/Kg/day), metformin and pioglitazone underwent super-selective injection of stem cells into superior pancreaticoduodenal artery under fluoroscopic guidance...
November 2014: Indian Journal of Endocrinology and Metabolism
M van de Vyver, E Andrag, I L Cockburn, W F Ferris
Chronic administration of the insulin-sensitising drugs, thiazolidinediones (TZDs), results in low bone mineral density and 'fatty bones'. This is thought to be due, at least in part, to aberrant differentiation of progenitor mesenchymal stem cells (MSCs) away from osteogenesis towards adipogenesis. This study directly compared the effects of rosiglitazone, pioglitazone, and netoglitazone treatment on osteogenesis and adipogenesis in MSCs derived from subcutaneous (SC) or visceral (PV) white adipose tissue...
November 2014: Journal of Endocrinology
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