PPAR-γ and Wnt Regulate the Differentiation of MSCs into Adipocytes and Osteoblasts Respectively

Li, Yue; Jin, Daxiang; Xie, Weixing; Wen, Longfei; Chen, Weijian; Xu, Jiamin; Ding, Jinyong; Ren, Dongcheng

doi:10.2174/1574888x12666171012141908

Cited by 126 publications

(92 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The interplay between PPAR‐γ and the Wnt signalling pathway has been extensively discussed. For example, the PPAR‐γ and Wnt pathways orchestrate the adipogenesis and osteogenesis of MSCs . Jiajian Liu, et al reported that the functional interaction between β‐catenin and PPAR‐γ involved the TCF/LEF‐binding domain of β‐catenin and a catenin‐binding domain (CBD) within PPAR‐γ .…”

Section: Discussionmentioning

confidence: 99%

“…For example, the PPAR-γ and Wnt pathways orchestrate the adipogenesis and osteogenesis of MSCs. 12 Jiajian Liu, et al reported that the functional interaction between β-catenin and PPAR-γ involved the TCF/LEF-binding domain of β-catenin and a catenin-binding domain (CBD) within PPAR-γ. 55 In this study, we substantiate the interaction between PPAR-γ and β-catenin by GW9662 intervention, indicating that Rb1 inhibited the Wnt/β-catenin pathway through the upstream activation of PPAR-γ.…”

Section: Discussionmentioning

confidence: 99%

“…PPAR‐γ is expressed in various cell types and regulates certain cellular metabolism and differentiation processes . The mutual antagonism between PPAR‐γ and the Wnt/β‐catenin pathway has been demonstrated to regulate the differentiation of mesenchymal stem cells (MSCs) into adipocytes and osteoblasts . In addition, pioglitazone, a PPAR‐γ agonist, has been suggested to inhibit the canonical Wnt pathway, which attenuates VC …”

Section: Introductionmentioning

confidence: 99%

“…11 The mutual antagonism between PPAR-γ and the Wnt/β-catenin pathway has been demonstrated to regulate the differentiation of mesenchymal stem cells (MSCs) into adipocytes and osteoblasts. 12 In addition, pioglitazone, a PPAR-γ agonist, has been suggested to inhibit the canonical Wnt pathway, which attenuates VC. 13 Ginsenosides are major components of the traditional herbal medicine ginseng, and ginsenosides can be classified into panaxadiols (PPD) and panaxatriols (PPT) by chemical structure.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Ginsenoside Rb1 ameliorates CKD‐associated vascular calcification by inhibiting the Wnt/β‐catenin pathway

Zhou

Zhang

Guo

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Vascular calcification (VC) is a pathological process underpinning major cardiovascular conditions and has attracted public attention due to its high morbidity and mortality. Chronic kidney disease (CKD) is a common disease related to VC. Ginsenoside Rb1 (Rb1) has been reported to protect the cardiovascular system against vascular diseases, yet its role in VC and the underlying mechanisms remain unclear. In this study, we established a CKD‐associated VC rat model and a β‐glycerophosphate (β‐GP)‐induced vascular smooth muscle cell (VSMC) calcification model to investigate the effects of Rb1 on VC. Our results demonstrated that Rb1 ameliorated calcium deposition and VSMC osteogenic transdifferentiation both in vivo and in vitro. Rb1 treatment inhibited the Wnt/β‐catenin pathway by activating peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), and confocal microscopy was used to show that Rb1 inhibited β‐catenin nuclear translocation in VSMCs. Furthermore, SKL2001, an agonist of the Wnt/β‐catenin pathway, compromised the vascular protective effect of Rb1. GW9662, a PPAR‐γ antagonist, reversed Rb1's inhibitory effect on β‐catenin. These results indicate that Rb1 exerted anticalcific properties through PPAR‐γ/Wnt/β‐catenin axis, which provides new insights into the potential theraputics of VC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Ginsenoside Rb1 ameliorates CKD‐associated vascular calcification by inhibiting the Wnt/β‐catenin pathway

Zhou

Zhang

Guo

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…In SrRN and CQ groups, the β-catenin protein level was obviously higher than in the induction group, which suggested that β-catenin itself might be targeted by autophagic clearance upon adipogenic induction. Since there was an internal crosstalk between β-catenin and PPAR-γ, which suggested that β-catenin might inhibit the expression of PPAR-γ in the differentiated lineage [4,24], the antiadipocytic effect of SrRN might be dependent on stabilization of the protein β-catenin.…”

Section: Discussionmentioning

confidence: 99%

Strontium ranelate-induced anti-adipocytic effects are involved in negative regulation of autophagy in rat bone marrow mesenchymal stem cells

Bai

2018

International Orthopaedics (SICOT)

View full text Add to dashboard Cite

Purposes Strontium ranelate (SrRN) is a novel and effective anti-osteoporotic drug used to promote bone formation and restrain bone resorption. However, studies of the effects and mechanism of SrRN on adipocytic differentiation from bone marrow mesenchymal stem cells (BMMSCs) remain limited. Methods The cytoactivity of BMMSCs was analyzed by CCK-8 and annexin V-FITC/PI kit. Then the differentiation efficiency was analyzed by Oil Red O staining and western blotting. The level of autophagy was evaluated by immunofluorescence and western blotting. The autophagy inhibitor chloroquine and the selective Akt antagonist API-2 were used to study the relationship between autophagy regulation and adipocytic differentiation. Finally variations in β-catenin protein levels were also analyzed by western blotting, as were proteins related with autophagy and differentiation signaling pathways. Results SrRN had no influence on the vatility of BMMSCs (bone marrow mesenchymal stem cells) and exhibited anti-adipocytic effects in dose-dependent manner. At the early stage of adipocytic differentiation, autophagy level significantly increased and SrRN inhibited the variation tendency. Then we detected the PPAR-γ and β-catenin variation when applied with autophagy inhibitor CQ (chloroquine) and the same way, after Akt selective inhibitor applied in the test, the effect of SrRN was compromised. At last, we detected the increased phosphorylation of Akt-related pathway at 1.00 mM concentration of SrRN in comparison with the adipocytic induction. Conclusions SrRN could disturb the process of adipocytic differentiation of BMMSCs and interfere with the variation tendency of autophagy level after adipocytic induction in Akt-dependent manners.

show abstract

New‐QiangGuYin‐Containing Serum Inhibits Osteoclast‐Derived Exosome Secretion and Down‐Regulates Notum to Promote Osteoblast Differentiation

Meng,

Zhang,

et al. 2024

Advanced Biology

View full text Add to dashboard Cite

New‐QiangGuYin (N‐QGY), the addition of sea buckthorn on the basis of QGY formula, is herbal formula widely used clinically in China for the treatment of osteoporosis (OP), but its mechanism warrants further exploration. The mechanisms of QGY and N‐QGY in the treatment of OP are probed from the perspective of osteoclast‐osteoblast balance. Thirty Sprague‐Dawley rats are randomly divided into N‐QGY group, QGY group, and Control group. Beyond control rats that orally took normal saline, other rats are orally administered with isometric N‐QGY or QGY twice every day for 3 days. The drug‐containing serum and control serum are prepared and their effects on osteoclast‐derived exosome secretion are determined by bicinchoninic acid assay (BCA), nanoparticle tracking analysis, and Western blot. GW4869 and Interleukin‐1β (IL‐1β) are adopted as the exosome inhibitor and inducer, respectively. Exosome uptake, cell counting kit‐8, alkaline phosphatase (ALP) staining, alizarin red staining, enzyme‐linked immunosorbent assay, quantitative real‐time polymerase chain reaction, and Western blot are performed to examine the effects of altered osteoclast exosome content on osteogenic differentiation of mesenchymal stem cells (MSCs). N‐QGY, QGY, and GW4869 inhibit osteoclast‐derived exosome secretion and exosome uptake by MSCs, whereas IL‐1β exerted the opposite effects (p < 0.05). Different from IL‐1β, N‐QGY, QGY, and GW4869 partially elevated MSC viability, osteocalcin secretion, ALP, RUNX Family Transcription Factor 2 (RUNX2) and Osteopontin (OPN) expressions, and calcium deposition in the osteoclast‐MSCs coculture system (p < 0.05). Mechanically, osteoclasts increased Notum protein level but decreased β‐catenin level, which is enhanced by IL‐1β but is reversed by GW4869, QGY, and N‐QGY (p < 0.05). And the effect of N‐QGY is more conspicuous than that of QGY (P<0.05). N‐QGY‐containing serum inhibits exosome levels in osteoclasts, thereby enhancing osteogenic differentiation of MSCs via inhibition of Notum protein and promotion of β‐catenin protein.

show abstract

PPAR-γ and Wnt Regulate the Differentiation of MSCs into Adipocytes and Osteoblasts Respectively

Cited by 126 publications

References 0 publications

Ginsenoside Rb1 ameliorates CKD‐associated vascular calcification by inhibiting the Wnt/β‐catenin pathway

Ginsenoside Rb1 ameliorates CKD‐associated vascular calcification by inhibiting the Wnt/β‐catenin pathway

Strontium ranelate-induced anti-adipocytic effects are involved in negative regulation of autophagy in rat bone marrow mesenchymal stem cells

New‐QiangGuYin‐Containing Serum Inhibits Osteoclast‐Derived Exosome Secretion and Down‐Regulates Notum to Promote Osteoblast Differentiation

Contact Info

Product

Resources

About