Calcitriol combined with calcium chloride causes apoptosis in undifferentiated adipose tissue-derived human mesenchymal stem cells, but this effect decreases during adipogenic differentiation.

Autor: Pesarini JR; Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Maria Aparecida Pedrossian University Hospital, Brazilian Hospital Services Company (EBSERH), Federal University of Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil; Federal University of Mato Grosso do Sul (UFMS), Graduate Programme in Health and Development in the Central-West Region, School of Medicine (FAMED), Campo Grande, Mato Grosso do Sul, Brazil., Oliveira EJT; Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Maria Aparecida Pedrossian University Hospital, Brazilian Hospital Services Company (EBSERH), Federal University of Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil; State University of Londrina (UEL), Graduate Programme in Genetics and Molecular Biology, Department of General Biology, Londrina, Paraná, Brazil., Pessatto LR; Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Maria Aparecida Pedrossian University Hospital, Brazilian Hospital Services Company (EBSERH), Federal University of Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil; State University of Londrina (UEL), Graduate Programme in Genetics and Molecular Biology, Department of General Biology, Londrina, Paraná, Brazil., Rabacow APM; Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Maria Aparecida Pedrossian University Hospital, Brazilian Hospital Services Company (EBSERH), Federal University of Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil; Federal University of Mato Grosso do Sul (UFMS), Graduate Programme in Health and Development in the Central-West Region, School of Medicine (FAMED), Campo Grande, Mato Grosso do Sul, Brazil., Camassola M; Lutheran University of Brazil (ULBRA), Graduate Programme in Cellular and Molecular Biology Applied to Health, Canoas, Rio Grande do Sul, Brazil., Dos Santos BP; Lutheran University of Brazil (ULBRA), Graduate Programme in Cellular and Molecular Biology Applied to Health, Canoas, Rio Grande do Sul, Brazil; Laboratory of Tissue Engineering, Inserm U1026 - BioTis, University of Bordeaux, France., de Barros ME; Federal University of Grande Dourados (UFGD), Faculdade de Ciências da Vida, Rodovia Dourados, Km 12, 79800-000 Dourados, Mato Grosso do Sul, Brazil., Cantero WB; Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Maria Aparecida Pedrossian University Hospital, Brazilian Hospital Services Company (EBSERH), Federal University of Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil; Federal University of Mato Grosso do Sul (UFMS), Graduate Programme in Health and Development in the Central-West Region, School of Medicine (FAMED), Campo Grande, Mato Grosso do Sul, Brazil., Antoniolli-Silva ACMB; Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Maria Aparecida Pedrossian University Hospital, Brazilian Hospital Services Company (EBSERH), Federal University of Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil; Federal University of Mato Grosso do Sul (UFMS), Graduate Programme in Health and Development in the Central-West Region, School of Medicine (FAMED), Campo Grande, Mato Grosso do Sul, Brazil., Oliveira RJ; Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Maria Aparecida Pedrossian University Hospital, Brazilian Hospital Services Company (EBSERH), Federal University of Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil; Federal University of Mato Grosso do Sul (UFMS), Graduate Programme in Health and Development in the Central-West Region, School of Medicine (FAMED), Campo Grande, Mato Grosso do Sul, Brazil; State University of Londrina (UEL), Graduate Programme in Genetics and Molecular Biology, Department of General Biology, Londrina, Paraná, Brazil. Electronic address: rodrigo.oliveira@ufms.br.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2018 Dec; Vol. 108, pp. 914-924. Date of Electronic Publication: 2018 Sep 26.
DOI: 10.1016/j.biopha.2018.09.083
Abstrakt: Calcitriol, the bioactive hormone of vitamin D, is currently linked to several diseases, such as obesity and gain of adipose mass, due to its liposolubility and, consequently, its sequestration by adipocytes. As rates of obesity continue to increase, research on the biology of weight gain should be encouraged. This study evaluated the effects of calcitriol combined with CaCl 2 on adipose tissue-derived human mesenchymal stem cells. We evaluated the cytotoxicity of the combination by MTT assays, in which undifferentiated cells and cells undergoing adipogenic differentiation were tested for 7 and 14 days. The results demonstrated that the combination of calcitriol at the IC 50 and CaCl 2 at the IC 20 was effective at reducing the viability of mesenchymal stem cells, but with the progression of cell differentiation towards adipocytes, cell resistance to the cytotoxic effects increased. The percentages of dead cells were 88.29, 57.45 and 28.81% for undifferentiated cells and cells exposed to differentiation medium for 7 and 14 days, respectively. Undifferentiated cells were evaluated for apoptosis in response to the same combination using Annexin V assays, and a possible onset of programmed cell death in undifferentiated cells was detected. Additionally, the combination of the compounds altered the membrane permeability of undifferentiated cells by 16 percentage points and induced cell cycle arrest in S phase due to the accumulation of damage. An evaluation of gene expression revealed the overexpression of the GADD45 and ATM genes and the underexpression of the P21, P53, ATR, BCL-2, EIF2 AK3, IGF1R, DNAse-2, ATF, MAP3K4, ENGO-G, CASP3, CASP7 and CASP8 genes. Our results provide valuable insights into the biology of obesity and may contribute to the development of new anti-obesity therapies focusing on the inhibition of adipose tissue mesenchymal stem cell hyperplasia and adipogenic differentiation.
(Copyright © 2018 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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