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Wnt antagonist secreted frizzled-related protein 4 upregulates adipogenic differentiation in human adipose tissue-derived mesenchymal stem cells.

Visweswaran M, Schiefer L, Arfuso F, Dilley RJ, Newsholme P, Dharmarajan A - PLoS ONE (2015)

Bottom Line: We also examined the effect of Wnt inhibition using secreted frizzled-related protein 4 (sFRP4), which we have previously shown to be pro-apoptotic, anti-angiogenic, and anti-tumorigenic.Wnt stimulation in LiCl and BIO-treated ADSCs resulted in a significant reduction (2.7-fold and 12-fold respectively) in lipid accumulation as measured by Oil red O staining while Wnt inhibition with sFRP4 induced a 1.5-fold increase in lipid accumulation.In contrast, the expression of adipogenic proteins (PPARγ, C/EBPα, and acetyl CoA carboxylase) were decreased significantly with LiCl (by 1.6, 2.6, and 1.9-fold respectively) and BIO (by 7, 17, and 5.6-fold respectively) treatments.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia.

ABSTRACT
With more than 1.4 billion overweight or obese adults worldwide, obesity and progression of the metabolic syndrome are major health and economic challenges. To address mechanisms of obesity, adipose tissue-derived mesenchymal stem cells (ADSCs) are being studied to detail the molecular mechanisms involved in adipogenic differentiation. Activation of the Wnt signalling pathway has inhibited adipogenesis from precursor cells. In our study, we examined this anti-adipogenic effect in further detail stimulating Wnt with lithium chloride (LiCl) and 6-bromo indirubin 3'oxime (BIO). We also examined the effect of Wnt inhibition using secreted frizzled-related protein 4 (sFRP4), which we have previously shown to be pro-apoptotic, anti-angiogenic, and anti-tumorigenic. Wnt stimulation in LiCl and BIO-treated ADSCs resulted in a significant reduction (2.7-fold and 12-fold respectively) in lipid accumulation as measured by Oil red O staining while Wnt inhibition with sFRP4 induced a 1.5-fold increase in lipid accumulation. Furthermore, there was significant 1.2-fold increase in peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha (C/EBPα), and 1.3-fold increase in acetyl CoA carboxylase protein levels. In contrast, the expression of adipogenic proteins (PPARγ, C/EBPα, and acetyl CoA carboxylase) were decreased significantly with LiCl (by 1.6, 2.6, and 1.9-fold respectively) and BIO (by 7, 17, and 5.6-fold respectively) treatments. These investigations demonstrate interplay between Wnt antagonism and Wnt activation during adipogenesis and indicate pathways for therapeutic intervention to control this process.

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Differentiation of ADSCs visualised by staining techniques.(A) Intracellular lipid globules of adipogenically differentiated ADSCs stained positively by Oil Red O (B) Calcium deposition of osteogenically differentiated ADSCs stained positively by Alizarin Red, (C) Mineralization of osteogenically differentiated ADSCs stained positively by Von Kossa, (D) Glycosaminoglycan deposition of chondrogenically differentiated ADSCs stained positively by Alcian blue, and (E) Fibroblast morphology of undifferentiated ADSCs. Scale bar = 10μM.
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pone.0118005.g001: Differentiation of ADSCs visualised by staining techniques.(A) Intracellular lipid globules of adipogenically differentiated ADSCs stained positively by Oil Red O (B) Calcium deposition of osteogenically differentiated ADSCs stained positively by Alizarin Red, (C) Mineralization of osteogenically differentiated ADSCs stained positively by Von Kossa, (D) Glycosaminoglycan deposition of chondrogenically differentiated ADSCs stained positively by Alcian blue, and (E) Fibroblast morphology of undifferentiated ADSCs. Scale bar = 10μM.

Mentions: To confirm the multi-potent nature of these ADSC cultures, their differentiation into adipogenic (7 days), osteogenic (28 days), and chondrogenic (21 days) lineages was examined. The results of the lineage-specific staining at the end of the indicated differentiation period showed the presence of lipid droplets, calcium mineralisation and proteoglycan deposition in the adipogenic, osteogenic, and chondrogenic differentiation respectively (Fig. 1) confirming the ADSC tri-lineage differentiation capacity.


Wnt antagonist secreted frizzled-related protein 4 upregulates adipogenic differentiation in human adipose tissue-derived mesenchymal stem cells.

Visweswaran M, Schiefer L, Arfuso F, Dilley RJ, Newsholme P, Dharmarajan A - PLoS ONE (2015)

Differentiation of ADSCs visualised by staining techniques.(A) Intracellular lipid globules of adipogenically differentiated ADSCs stained positively by Oil Red O (B) Calcium deposition of osteogenically differentiated ADSCs stained positively by Alizarin Red, (C) Mineralization of osteogenically differentiated ADSCs stained positively by Von Kossa, (D) Glycosaminoglycan deposition of chondrogenically differentiated ADSCs stained positively by Alcian blue, and (E) Fibroblast morphology of undifferentiated ADSCs. Scale bar = 10μM.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4340908&req=5

pone.0118005.g001: Differentiation of ADSCs visualised by staining techniques.(A) Intracellular lipid globules of adipogenically differentiated ADSCs stained positively by Oil Red O (B) Calcium deposition of osteogenically differentiated ADSCs stained positively by Alizarin Red, (C) Mineralization of osteogenically differentiated ADSCs stained positively by Von Kossa, (D) Glycosaminoglycan deposition of chondrogenically differentiated ADSCs stained positively by Alcian blue, and (E) Fibroblast morphology of undifferentiated ADSCs. Scale bar = 10μM.
Mentions: To confirm the multi-potent nature of these ADSC cultures, their differentiation into adipogenic (7 days), osteogenic (28 days), and chondrogenic (21 days) lineages was examined. The results of the lineage-specific staining at the end of the indicated differentiation period showed the presence of lipid droplets, calcium mineralisation and proteoglycan deposition in the adipogenic, osteogenic, and chondrogenic differentiation respectively (Fig. 1) confirming the ADSC tri-lineage differentiation capacity.

Bottom Line: We also examined the effect of Wnt inhibition using secreted frizzled-related protein 4 (sFRP4), which we have previously shown to be pro-apoptotic, anti-angiogenic, and anti-tumorigenic.Wnt stimulation in LiCl and BIO-treated ADSCs resulted in a significant reduction (2.7-fold and 12-fold respectively) in lipid accumulation as measured by Oil red O staining while Wnt inhibition with sFRP4 induced a 1.5-fold increase in lipid accumulation.In contrast, the expression of adipogenic proteins (PPARγ, C/EBPα, and acetyl CoA carboxylase) were decreased significantly with LiCl (by 1.6, 2.6, and 1.9-fold respectively) and BIO (by 7, 17, and 5.6-fold respectively) treatments.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia.

ABSTRACT
With more than 1.4 billion overweight or obese adults worldwide, obesity and progression of the metabolic syndrome are major health and economic challenges. To address mechanisms of obesity, adipose tissue-derived mesenchymal stem cells (ADSCs) are being studied to detail the molecular mechanisms involved in adipogenic differentiation. Activation of the Wnt signalling pathway has inhibited adipogenesis from precursor cells. In our study, we examined this anti-adipogenic effect in further detail stimulating Wnt with lithium chloride (LiCl) and 6-bromo indirubin 3'oxime (BIO). We also examined the effect of Wnt inhibition using secreted frizzled-related protein 4 (sFRP4), which we have previously shown to be pro-apoptotic, anti-angiogenic, and anti-tumorigenic. Wnt stimulation in LiCl and BIO-treated ADSCs resulted in a significant reduction (2.7-fold and 12-fold respectively) in lipid accumulation as measured by Oil red O staining while Wnt inhibition with sFRP4 induced a 1.5-fold increase in lipid accumulation. Furthermore, there was significant 1.2-fold increase in peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha (C/EBPα), and 1.3-fold increase in acetyl CoA carboxylase protein levels. In contrast, the expression of adipogenic proteins (PPARγ, C/EBPα, and acetyl CoA carboxylase) were decreased significantly with LiCl (by 1.6, 2.6, and 1.9-fold respectively) and BIO (by 7, 17, and 5.6-fold respectively) treatments. These investigations demonstrate interplay between Wnt antagonism and Wnt activation during adipogenesis and indicate pathways for therapeutic intervention to control this process.

Show MeSH
Related in: MedlinePlus