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

Autor(es)

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Pharmacology; v. 911, NOV 15 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 15/03965-2 - Papel do sistema renina-angiotensina em diferentes modelos inflamatórios orais: uma abordagem interdisciplinar experimental e clínica
• Beneficiário: Carlos Ferreira dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/05873-3 - Análise in vitro do papel dos mastócitos e do sistema renina-angiotensina sobre osteoblastos e osteoclastos de animais espontaneamente hipertensos
• Beneficiário: Sabrina Cruz Tfaile Frasnelli
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado