Telmisartan impairs the in vitro osteogenic differentiation of mesenchymal stromal cells from spontaneously hypertensive male rats

Author(s)

Brito, Victor Gustavo Balera ^{[1, 2]} ; Patrocinio, Mariana Sousa ^[1] ; Barreto, Ayna Emanuelli Alves ^{[1, 2]} ; Frasnelli, Sabrina Cruz Tfaile ^[1] ; Lara, Vanessa Soares ^[3] ; Santos, Carlos Ferreira ^[4] ; Oliveira, Sandra Helena Penha ^{[1, 2]}

Affiliation

^[1] Sao Paulo State Univ UNESP, Sch Dent, Dept Basic Sci, Aracatuba, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Brazilian Soc Physiol, Sch Dent, Multictr Postgrad Program Physiol Sci, Aracatuba, SP - Brazil

^[3] Univ Sao Paulo, Bauru Sch Dent, Dept Stomatol, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Bauru Sch Dent, Dept Biol Sci, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: European Journal of Pharmacology; v. 912, DEC 5 2021.
• Web of Science Citations: 0

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 mu M). 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 mu M 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. (AU)

• FAPESP's process: 17/02271-2 - The role of Telmisartan in osteoblastic differentiation in spontaneously hypertensive rats
• Grantee: Mariana Sousa Patrocinio
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 15/03965-2 - Role of the renin-angiotensin system in different oral inflammatory models: an experimental interdisciplinary and clinical approach
• Grantee: Carlos Ferreira dos Santos
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/05873-3 - In vitro analysis of mast cells and renin-angiotensin system role of spontaneously hypertensive animals osteoblasts and osteoclasts
• Grantee: Sabrina Cruz Tfaile Frasnelli
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/23676-3 - MicroRNAs role in bone impairment induced by periodontal disease and the local renin-angiotensin system in spontaneous hypertensive rats
• Grantee: Victor Gustavo Balera Brito
• Support Opportunities: Scholarships in Brazil - Doctorate