PMID- 34555397
OWN - NLM
STAT- MEDLINE
DCOM- 20220204
LR  - 20220204
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 911
DP  - 2021 Nov 15
TI  - beta1-adrenergic receptor but not beta2 mediates osteogenic differentiation of bone 
      marrow mesenchymal stem cells in normotensive and hypertensive rats.
PG  - 174515
LID - S0014-2999(21)00669-5 [pii]
LID - 10.1016/j.ejphar.2021.174515 [doi]
AB  - 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 beta-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.
CI  - Copyright (c) 2021. Published by Elsevier B.V.
FAU - Alves Barreto, Ayna Emanuelli
AU  - Alves Barreto AE
AD  - Department of Basic Sciences, School of Dentistry of Aracatuba, Sao Paulo State 
      University (UNESP), Sao Paulo, Brazil; Programa Multicentrico de Pos-Graduacao em 
      Ciencias Fisiologicas - SBFis/UNESP, Brazil; Department of Basic Sciences, Sao 
      Paulo State University (UNESP), School of Dentistry of Aracatuba, Sao Paulo, 
      Brazil.
FAU - Balera Brito, Victor Gustavo
AU  - Balera Brito VG
AD  - Department of Basic Sciences, School of Dentistry of Aracatuba, Sao Paulo State 
      University (UNESP), Sao Paulo, Brazil; Programa Multicentrico de Pos-Graduacao em 
      Ciencias Fisiologicas - SBFis/UNESP, Brazil; Department of Basic Sciences, Sao 
      Paulo State University (UNESP), School of Dentistry of Aracatuba, Sao Paulo, 
      Brazil.
FAU - Patrocinio, Mariana Sousa
AU  - Patrocinio MS
AD  - Department of Basic Sciences, School of Dentistry of Aracatuba, Sao Paulo State 
      University (UNESP), Sao Paulo, Brazil.
FAU - Ballassoni, Beatriz Babeto
AU  - Ballassoni BB
AD  - Department of Basic Sciences, School of Dentistry of Aracatuba, Sao Paulo State 
      University (UNESP), Sao Paulo, Brazil.
FAU - Tfaile Frasnelli, Sabrina Cruz
AU  - Tfaile Frasnelli SC
AD  - Department of Basic Sciences, School of Dentistry of Aracatuba, Sao Paulo State 
      University (UNESP), Sao Paulo, Brazil.
FAU - Penha Oliveira, Sandra Helena
AU  - Penha Oliveira SH
AD  - Department of Basic Sciences, School of Dentistry of Aracatuba, Sao Paulo State 
      University (UNESP), Sao Paulo, Brazil; Programa Multicentrico de Pos-Graduacao em 
      Ciencias Fisiologicas - SBFis/UNESP, Brazil; Department of Basic Sciences, Sao 
      Paulo State University (UNESP), School of Dentistry of Aracatuba, Sao Paulo, 
      Brazil. Electronic address: sandra.hp.oliveira@unesp.br.
LA  - eng
PT  - Journal Article
DEP - 20210920
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
SB  - IM
MH  - *Osteogenesis
OTO - NOTNLM
OT  - Hypertensive rats
OT  - Normotensive
OT  - Osteogenic differentiation
OT  - beta-adrenergic receptor
EDAT- 2021/09/24 06:00
MHDA- 2022/02/05 06:00
CRDT- 2021/09/23 20:12
PHST- 2021/05/20 00:00 [received]
PHST- 2021/09/10 00:00 [revised]
PHST- 2021/09/17 00:00 [accepted]
PHST- 2021/09/24 06:00 [pubmed]
PHST- 2022/02/05 06:00 [medline]
PHST- 2021/09/23 20:12 [entrez]
AID - S0014-2999(21)00669-5 [pii]
AID - 10.1016/j.ejphar.2021.174515 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2021 Nov 15;911:174515. doi: 10.1016/j.ejphar.2021.174515. Epub 
      2021 Sep 20.