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The Role of Calcium in Differentiation of Human Adipose-Derived Stem Cells to Adipocytes

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Abstract

Differentiation process of mesenchymal stem cells (MSCs) into adipocyte is involved in obesity. Multiple factors such as Ca2+ play important roles in different stages of this process. Because of the complicated roles of Ca2+ in adipogenesis, the aim of present investigation was to study the influx and efflux of Ca2+ into and out of the cells during adipogenesis. Adipose-derived MSCs were used to differentiate into adipocytes. MSCs were exposed to 2.5 mM Ca2+ or 1.8 mM Ca2+ plus calcium ionophore, A23187, for 3 days. Lipid staining, triglycerides (TG) content, and glyceraldehyde phosphate dehydrogenase (GAPDH) activity were evaluated to confirm the efficiency of the differentiation. Gene expression of GLUT4, PPARγ2, RAR-α, and calreticulin, as well as the protein levels of GLUT4 and PPARγ2 were determined. Ca2+ and in particular Ca2+ plus A23187 significantly lowered the efficiency of differentiation accompanied by decrease in intracellular TG deposits, GAPDH activity and alleviation of gene, and protein levels of GLUT4 and PPARγ2. While calreticulin and RAR-α were remarkably upregulated in A23187 group. This study showed the inhibitory effects of calcium in adipogenesis. Additionally, it indicated the greater inhibitory effect of calreticulin and RAR-α in controlling adipogenesis by higher levels of calcium.

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Abbreviations

MSCs:

Mesenchymal stem cells

PPARγ:

Peroxisome proliferator-activated receptor gamma

C/EBP:

CCAAT/enhancer-binding protein

FAS:

Fatty acid synthase

ADSCs:

Adipose-derived stem cells

IBMX:

3-Isobutyl-1-methylxanthine

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

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Acknowledgements

We thank Hamadan University of Medical Sciences for financial support (Grant No. 9406173346) and aids.

Authors’ Contribution

FG carried out the experiments. MTG and AM were involved in experimental design and manuscript draft preparation. SK, RM, and MB participated in the collection and/or assembly of data. IK interpreted the molecular biological data and modified the language of the draft manuscript. All the authors read and approved the final manuscript.

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Authors and Affiliations

  1. Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Farjam Goudarzi

  2. Department of Clinical Biochemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

    Adel Mohammadalipour

  3. Department of Clinical Biochemistry, Faculty of Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Iraj Khodadadi, Rezvan Mostoli, Majid Bahabadi & Mohammad Taghi Goodarzi

  4. Department of Nutrition Sciences, School of Nutrition and Food Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Sheno Karimi

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  1. Farjam Goudarzi
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Correspondence to Mohammad Taghi Goodarzi.

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The study was approved by the Ethics Committee of Hamadan University of Medical Sciences.

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Goudarzi, F., Mohammadalipour, A., Khodadadi, I. et al. The Role of Calcium in Differentiation of Human Adipose-Derived Stem Cells to Adipocytes. Mol Biotechnol 60, 279–289 (2018). https://doi.org/10.1007/s12033-018-0071-x

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