Arsenic inhibits the adipogenic differentiation of mesenchymal stem cells by down-regulating peroxisome proliferator-activated receptor gamma and CCAAT enhancer-binding proteins

2013 ◽  
Vol 27 (1) ◽  
pp. 211-219 ◽  
Author(s):  
Santosh Yadav ◽  
Muralidharan Anbalagan ◽  
Yongli Shi ◽  
Feng Wang ◽  
He Wang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Binding Proteins ◽  
Adipogenic Differentiation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Enhancer Binding Proteins

Regulation of adipocyte differentiation of 3T3-L1 cells by PDZRN3

2013 ◽  
Vol 304 (11) ◽  
pp. C1091-C1097 ◽  
Author(s):  
Takeshi Honda ◽  
Aiko Ishii ◽  
Makoto Inui
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipocyte Differentiation ◽  
Early Stage ◽  
Adipogenic Differentiation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Upstream Regulator ◽  
Pparγ Expression

PDZRN3, a member of the PDZRN (or LNX) family of proteins, is essential for the differentiation of mesenchymal stem cells into myotubes, but it plays an inhibitory role in the differentiation of these cells into osteoblasts. Given that mesenchymal stem cells also differentiate into adipocytes, we examined the possible role of PDZRN3 in adipogenesis in mouse 3T3-L1 preadipocytes. The expression of PDZRN3 decreased at both the mRNA and protein levels during adipogenic differentiation. RNAi-mediated depletion of PDZRN3 enhanced the differentiation of 3T3-L1 cells into adipocytes as assessed on the basis of lipid accumulation. The upregulation of aP2 and CCAAT/enhancer-binding protein (C/EBP)-β during adipocyte differentiation was also enhanced in the PDZRN3-depleted cells, as was the induction of peroxisome proliferator-activated receptor-γ (PPARγ), an upstream regulator of aP2 and C/EBPα, at both the mRNA and protein levels. Among transcription factors that control the expression of PPARγ, we found that STAT5b, but not STAT5a, was upregulated in PDZRN3-depleted cells at both mRNA and protein levels. Tyrosine phosphorylation of STAT5b, but not that of STAT5a, was also enhanced at an early stage of differentiation by PDZRN3 depletion. In addition, the expression of C/EBPβ during the induction of differentiation was enhanced at the mRNA and protein levels in PDZRN3-depleted cells. Our results thus suggest that PDZRN3 negatively regulates adipogenesis in 3T3-L1 cells through downregulation of STAT5b and C/EBPβ and consequent suppression of PPARγ expression.

scholarly journals Bisphenol A enhances adipogenic differentiation of human adipose stromal/stem cells

2014 ◽  
Vol 53 (3) ◽  
pp. 345-353 ◽  
Author(s):  
Jason F Ohlstein ◽  
Amy L Strong ◽  
John A McLachlan ◽  
Jeffrey M Gimble ◽  
Matthew E Burow ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bisphenol A ◽  
Leucine Zipper ◽  
Adipogenic Differentiation ◽  
Density Measurement ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Enhancer Binding Protein ◽  
Pm 10 ◽  
Stromal Stem Cells

Exposure of humans to the endocrine disrupter bisphenol A (BPA) has been associated with increased weight and obesity. However, the mechanism(s) by which BPA increases adipose tissue in humans remains to be determined. The goal of this study was to determine the effects of BPA on adipogenesis of cultured human adipose stromal/stem cells (ASCs), precursors to mature adipocytes. ASCs from three donors were cultured for either 14 or 21 days in adipogenic differentiation media containing increasing concentrations of BPA (100 pM–10 μM). The extent of adipogenic differentiation in the ASCs was assessed by staining with Oil Red O to visualize adipogenic differentiation and then quantified by extraction and optical density measurement of the retained dye. BPA significantly enhanced adipogenesis at a concentration of 1 μM after 21 days of culture. Additionally, we found that BPA increased transcription of the estrogen receptor (ER (ESR1)) and that treatment with the ER antagonist ICI 182 780, blocked the effects of BPA, indicating that BPA may act via an ER-mediated pathway. The results of molecular analyses indicated that the expression of the adipogenesis-associated genes dual leucine zipper-bearing kinase (DLK (MAP3K12)), IGF1, CCAAT/enhancer-binding protein alpha (C/EBPα (CEBPA)), peroxisome proliferator-activated receptor gamma (PPARγ (PPARG)), and lipoprotein lipase (LPL) was temporally accelerated and increased by BPA. In summary, these results indicate that BPA significantly enhances adipogenesis in ASCs through an ER-mediated pathway at physiologically relevant concentrations.

scholarly journals Recovery of Tendon Characteristics by Inhibition of Aberrant Differentiation of Tendon-Derived Stem Cells from Degenerative Tendinopathy

2020 ◽  
Vol 21 (8) ◽  
pp. 2687 ◽  
Author(s):  
Sun Jeong Kim ◽  
Hae Won Oh ◽  
Jong Wook Chang ◽  
Sang Jun Kim
Keyword(s):  
Stem Cells ◽  
Adipogenic Differentiation ◽  
Optimal Dose ◽  
Specific Marker ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Tenogenic Differentiation ◽  
Chemically Induced ◽  
Related Transcription Factor

The inhibition of the aberrant differentiation of tendon-derived stem cells (TDSCs) is a major target for the regeneration of damaged tendon tissues, as tendinopathy can be caused by the aberrant differentiation of TDSCs. We investigated whether the possible aberrant differentiation of TDSCs can be prevented by using adequate inhibitors. TDSCs extracted from chemically induced tendinopathy and injury-with-overuse tendinopathy models were cultured with 18α-glycyrrhetinic acid (AGA) and T0070907 to block osteogenic differentiation and adipogenic differentiation, respectively. The optimal dose of AGA decreased the osteogenic-specific marker Runx2 (Runt-related transcription factor 2), and T0070907 blocked the adipogenic-specific marker peroxisome proliferator-activated receptor gamma (PPARγ) in mRNA levels. We also found that AGA induced tenogenic differentiation in mRNA levels. However, T0070907 did not affect the tenogenic differentiation and regenerative capacity of TDSCs. We expect that optimal doses of AGA and T0070907 can prevent tendinopathy by inhibiting osteogenic and adipogenic differentiation, respectively. In addition, AGA and T0070907 may play important roles in the treatment of tendinopathy.

scholarly journals Simulated Microgravity Suppresses Osteogenic Differentiation of Mesenchymal Stem Cells by Inhibiting Oxidative Phosphorylation

2020 ◽  
Vol 21 (24) ◽  
pp. 9747
Author(s):  
Lin Liu ◽  
Yansiwei Cheng ◽  
Jie Wang ◽  
Zhongjie Ding ◽  
Alexander Halim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Energy Metabolism ◽  
Oxidative Phosphorylation ◽  
Osteogenic Differentiation ◽  
Simulated Microgravity ◽  
Sirtuin 1 ◽  
Peroxisome Proliferator ◽  
Mtdna Copy Number ◽  
Peroxisome Proliferator Activated Receptor

Studies showed that energy metabolism plays a pivotal role in the differentiation of stem cells. Previous studies revealed that simulated microgravity (SMG) inhibits osteogenic differentiation of mesenchymal stem cells (MSCs). However, the underlying relationship between osteogenesis and energy metabolism under SMG conditions is not fully understood. In the present study, we investigated mitochondrial oxidative phosphorylation (OXPHOS) by assessing the level of peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α), mitochondrial DNA (mtDNA) copy number, mitochondrial mass and oxygen consumption rate (OCR) during osteogenesis of MSCs under SMG conditions. We found that SMG inhibited osteogenic differentiation and OXPHOS of MSCs. Moreover, the expression of sirtuin 1 (Sirt1), an important energy sensor, significantly decreased. After upregulating the expression of Sirt1 using resveratrol, an activator of Sirt1, SMG-inhibited OXPHOS and osteogenic differentiation of MSCs were recovered. Taken together, our results suggest that SMG suppresses osteogenic differentiation of MSCs by inhibiting OXPHOS, indicating that OXPHOS might serve as a potential therapeutic target for repairing bone loss under microgravity conditions.

Sign in / Sign up

Export Citation Format

Share Document