scholarly journals Noggin Is Novel Inducer of Mesenchymal Stem Cell Adipogenesis

2012 ◽  
Vol 287 (15) ◽  
pp. 12241-12249 ◽  
Author(s):  
Anandi Sawant ◽  
Diptiman Chanda ◽  
Tatyana Isayeva ◽  
George Tsuladze ◽  
W. T. Garvey ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bmp Signaling ◽  
Peroxisome Proliferator ◽  
Inhibitory Effects ◽  
Immunocompetent Mouse ◽  
Peroxisome Proliferator Activated Receptor ◽  
Morphogenetic Protein ◽  
First Time

Noggin is a glycosylated-secreted protein known so far for its inhibitory effects on bone morphogenetic protein (BMP) signaling by sequestering the BMP ligand. We report here for the first time a novel mechanism by which noggin directly induces adipogenesis of mesenchymal stem cells independently of major human adipogenic signals through C/EBPδ, C/EBPα and peroxisome proliferator-activated receptor-γ. Evaluation of a possible mechanism for noggin-induced adipogenesis of mesenchymal stem cells identified the role of Pax-1 in mediating such differentiation. The relevance of elevated noggin levels in obesity was confirmed in a preclinical, immunocompetent mouse model of spontaneous obesity and in human patients with higher body mass index. These data clearly provide a novel role for noggin in inducing adipogenesis and possibly obesity and further indicates the potential of noggin as a therapeutic target to control obesity.

scholarly journals Mechanical Strain Inhibits Adipogenesis in Mesenchymal Stem Cells by Stimulating a Durable β-Catenin Signal

Endocrinology ◽  
2008 ◽  
Vol 149 (12) ◽  
pp. 6065-6075 ◽  
Author(s):  
Buer Sen ◽  
Zhihui Xie ◽  
Natasha Case ◽  
Meiyun Ma ◽  
Clinton Rubin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Glycogen Synthase ◽  
Mechanical Strain ◽  
Bone Morphogenetic Protein 2 ◽  
Peroxisome Proliferator ◽  
Glycogen Synthase Kinase 3Β ◽  
Peroxisome Proliferator Activated Receptor ◽  
Morphogenetic Protein ◽  
Adiponectin Mrna

The ability of exercise to decrease fat mass and increase bone mass may occur through mechanical biasing of mesenchymal stem cells (MSCs) away from adipogenesis and toward osteoblastogenesis. C3H10T1/2 MSCs cultured in highly adipogenic medium express peroxisome proliferator-activated receptor γ and adiponectin mRNA and protein, and accumulate intracellular lipid. Mechanical strain applied for 6 h daily inhibited expression of peroxisome proliferator-activated receptor γ and adiponectin mRNA by up to 35 and 50%, respectively, after 5 d. A decrease in active and total β-catenin levels during adipogenic differentiation was entirely prevented by daily application of mechanical strain; furthermore, strain induced β-catenin nuclear translocation. Inhibition of glycogen synthase kinase-3β by lithium chloride or SB415286 also prevented adipogenesis, suggesting that preservation of β-catenin levels was important to strain inhibition of adipogenesis. Indeed, mechanical strain inactivated glycogen synthase kinase-3β, which was preceded by Akt activation, indicating that strain transmits antiadipogenic signals through this pathway. Cells grown under adipogenic conditions showed no increase in osteogenic markers runt-related transcription factor (Runx) 2 and osterix (Osx); subsequent addition of bone morphogenetic protein 2 for 2 d increased Runx2 but not Osx expression in unstrained cultures. When cultures were strained for 5 d before bone morphogenetic protein 2 addition, Runx2 mRNA increased more than in unstrained cultures, and Osx expression more than doubled. As such, mechanical strain enhanced MSC potential to enter the osteoblast lineage despite exposure to adipogenic conditions. Our results indicate that MSC commitment to adipogenesis can be suppressed by mechanical signals, allowing other signals to promote osteoblastogenesis. These data suggest that positive effects of exercise on both fat and bone may occur during mesenchymal lineage selection.

scholarly journals The role of signal transducer and activator of transcription 5 in the inhibitory effects of GH on adipocyte differentiation

2003 ◽  
Vol 30 (2) ◽  
pp. 139-150 ◽  
Author(s):  
HE Richter ◽  
T Albrektsen ◽  
N Billestrup
Keyword(s):  
Tyrosine Phosphorylation ◽  
Janus Kinase ◽  
Peroxisome Proliferator ◽  
Transactivation Domain ◽  
Signal Transducer ◽  
Inhibitory Effects ◽  
Preadipocyte Differentiation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding

GH inhibits primary rat preadipocyte differentiation and expression of late genes required for terminal differentiation. Here we show that GH-mediated inhibition of fatty acid-binding protein aP2 gene expression correlates with the activation of the Janus kinase-2/signal transducer and activator of transcription (STAT)-5 signalling pathway. Within minutes of treatment, GH induced the tyrosine phosphorylation, nuclear localization and DNA binding of STAT5. Importantly, there was no evidence that STAT5 acted via an interaction with peroxisome proliferator-activated receptor gamma. To further understand the mechanism of STAT5 action, we reconstituted the inhibition of aP2 in a non-adipogenic cell line. Using this system, we showed that the ability of GH to inhibit a 520 bp aP2 reporter was largely dependent upon the presence of either STAT5A or STAT5B. Mutant analysis confirmed that the tyrosine phosphorylation of STAT5 was essential for this signalling. However, STAT5's C-terminal transactivation domain was fully dispensable for this inhibition. Taken together, these data confirm a key regulatory role of STAT5 in adipose tIssue and point to STAT5 as the repressing modulator of GH-mediated inhibition in primary preadipocytes.

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.

scholarly journals UHRF1 Promotes Proliferation of Human Adipose-Derived Stem Cells and Suppresses Adipogenesis via Inhibiting Peroxisome Proliferator-Activated Receptor γ

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Ke Chen ◽  
Zi Guo ◽  
Yufang Luo ◽  
Jingjing Yuan ◽  
Zhaohui Mo
Keyword(s):  
Stem Cells ◽  
Ring Finger ◽  
Cell Counting ◽  
Peroxisome Proliferator ◽  
Adipose Derived Stem Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Proliferation And Differentiation ◽  
Oil Red O Staining ◽  
Oil Red O

Once the adipose tissue is enlarged for the purpose of saving excess energy intake, obesity may be observed. Ubiquitin-like with PHD and RING Finger domains 1 (UHRF1) is helpful in repairing damaged DNA as it increases the resistance of cancer cells against cytocidal drugs. Peroxisome proliferator-activated receptor γ (PPARγ), an important nucleus transcription factor participating in adipogenesis, has been extensively reported. To date, no study has indicated whether UHRF1 can regulate proliferation and differentiation of human adipose-derived stem cells (hADSCs). Hence, this study aimed to utilize overexpression or downregulation of UHRF1 to explore the possible mechanism of proliferation and differentiation of hADSCs. We here used lentivirus, containing UHRF1 (LV-UHRF1) and siRNA-UHRF1 to transfect hADSCs, on which Cell Counting Kit-8 (CCK-8), cell growth curve, colony formation assay, and EdU proliferation assay were applied to evaluate proliferation of hADSCs, cells cycle was investigated by flow cytometry, and adipogenesis was detected by Oil Red O staining and Western blotting. Our results showed that UHRF1 can promote proliferation of hADSCs after overexpression of UHRF1, while proliferation of hADSCs was reduced through downregulation of UHRF1, and UHRF1 can control proliferation of hADSCs through transition from G1-phase to S-phase; besides, we found that UHRF1 negatively regulates adipogenesis of hADSCs via PPARγ. In summary, the results may provide a new insight regarding the role of UHRF1 on regulating proliferation and differentiation of hADSCs.

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