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Telmisartan impairs the in vitro osteogenic differentiation of mesenchymal stromal cells from spontaneously hypertensive male rats.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2021 Dec 05; Vol. 912, pp. 174609. Date of Electronic Publication: 2021 Oct 29. - Publication Year :
- 2021
-
Abstract
- Telmisartan (TELM) is an angiotensin II (Ang II) type 1 receptor (Agtr1) antagonist, with partial agonism for Pparg, and has been shown to affect bone metabolism. Therefore, the aim of this study was to investigate the effects of TELM in the in vitro osteogenic differentiation of bone marrow-derived mesenchymal stromal cells (BMSC) from spontaneously hypertensive rats (SHRs). BMSC were obtained from male SHR, and the osteogenic medium (OM) was added to the cells concomitantly with TELM (0.005, 0.05, and 0.5 μM). Undifferentiated BMSC, in control medium (CM), showed an increased viability, while the addition of OM reduced this parameter, and TELM did not show cytotoxicity in the concentrations used. BMSC in OM had an alkaline phosphatase (ALP) activity peak at d10, which decreased at d14 and d21, and TELM reduced ALP at d10 in a dose-dependent manner. Mineralization was observed in the OM at d14, which intensified at d21, but was inhibited by TELM. Agtr1b was increased in the OM, and TELM inhibited its expression. TELM reduced Opn, Ocn, and Bsp and increased Pparg expression, and at the higher concentration TELM also increased the expression of adipogenic markers, Fabp4 and Adipoq. In addition, TELM 0.5 μM increased Irs1 and Glut4, insulin and glucose metabolism markers, known to be regulated by Pparg and to be related to adipogenic phenotype. Our data shows that TELM inhibited the osteogenic differentiation and mineralization of SHR BMSC, by favoring an adipogenic prone phenotype due to Pparg upregulation.<br /> (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Subjects :
- Adipogenesis drug effects
Adipogenesis genetics
Alkaline Phosphatase metabolism
Animals
Calcification, Physiologic drug effects
Extracellular Matrix metabolism
Male
PPAR gamma metabolism
Rats, Inbred SHR
Receptors, Angiotensin genetics
Receptors, Angiotensin metabolism
Rats
Cell Differentiation drug effects
Mesenchymal Stem Cells drug effects
Osteogenesis drug effects
Telmisartan pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 912
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 34743978
- Full Text :
- https://doi.org/10.1016/j.ejphar.2021.174609