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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

beta 1-adrenergic receptor but not beta 2 mediates osteogenic differentiation of bone marrow mesenchymal stem cells in normotensive and hypertensive rats

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Barreto, Ayna Emanuelli Alves [1, 2] ; Brito, Victor Gustavo Balera [1, 2] ; Patrocinio, Mariana Sousa [1] ; Ballassoni, Beatriz Babeto [1] ; Frasnelli, Sabrina Cruz Tfaile [1] ; Oliveira, Sandra Helena Penha [1, 2]
Total Authors: 6
[1] Sao Paulo State Univ UNESP, Sch Dent Aracatuba, Dept Basic Sci, Sao Paulo - Brazil
[2] Sao Paulo State Univ UNESP, Sch Dent Aracatuba, Dept Basic Sci, Programa Multicentr Posgrad Ciencias Fisiol SBFis, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: European Journal of Pharmacology; v. 911, NOV 15 2021.
Web of Science Citations: 0

The sympathetic nervous system regulates bone remodeling via adrenergic receptors on the surface of bone cells. Herein, we evaluated the role of beta-adrenergic receptors (ADRBs) in osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs) derived from normotensive (Wistar) and spontaneously hypertensive rats (SHRs). BMSCs were cultured in a proliferation medium or osteogenic medium (OM). Cells cultured in OM were treated with carvedilol (Cv) or nebivolol (Nb). In OM, cell proliferation was decreased in both strains. In Wistar rats, Cv increased BMSC proliferation and increased alkaline phosphatase (ALP) activity in OM. Both Cv and Nb decreased ALP activity. In addition, Cv and Nb reduced mineral deposition in Wistar rats. Moreover, NB decreased mineralization in SHRs, exhibiting superior efficacy. In OM, cells from Wistar rats and SHRs showed Adrb1 and Adrb2 expression. On day 7, Nb, but not Cv, reduced Adrb1 levels in BMSCs from Wistar rats. Nb inhibited Adrb2 in both strains, and Cv demonstrated superior efficacy. In BMSCs from Wistar rats, both antagonists inhibited Runx2, osterix, and 8-catenin; in SHRs, Cv and Nb inhibited only osterix. Cv decreased osteopontin (Opn), osteocalcin (Ocn), and bone morphogenetic protein (Bmp2) in BMSCs from Wistar rats, inhibiting only Opn in SHRs. Nb effectively inhibited Ocn, bone sialoprotein, and Bmp2, but not Ocn, in BMSCs from Wistar rats, while suppressing Opn in BMSCs from SHRs. In addition, Nb inhibited p-p38 in BMSCs from Wistar rats; Cv inhibited p-p38 in BMSCs from SHRs. In Wistar rats, both antagonists inhibited p-ERK and reduced p-JNK; Cv reduced these expressions only in SHRs. In conclusion, ADRB1, but not ADRB2, could be involved in the osteogenic differentiation of BMSCs from Wistar rats and SHRs. The high ADRB1 expression might suppress the effect of ADRB2 on BMSCs. (AU)

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