miRNA Mechanisms Underlying the Association of Beta Blocker Use and Bone Mineral Density.
BETA BLOCKERS
BONE MINERAL DENSITY
DXA
OSTEOPOROSIS
miRNA
Journal
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
ISSN: 1523-4681
Titre abrégé: J Bone Miner Res
Pays: United States
ID NLM: 8610640
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
13
12
2019
revised:
25
07
2020
accepted:
05
08
2020
pubmed:
14
8
2020
medline:
29
7
2021
entrez:
14
8
2020
Statut:
ppublish
Résumé
Osteoporosis is a debilitating and costly disease that causes fractures in 33% of women and 20% of men over the age of 50 years. Recent studies have shown that beta blocker (BB) users have higher bone mineral density (BMD) and decreased risk of fracture compared with non-users. The mechanism underlying this association is thought to be due to suppression of adrenergic signaling in osteoblasts, which leads to increased BMD in rodent models; however, the mechanism in humans is unknown. Also, several miRNAs are associated with adrenergic signaling and BMD in separate studies. To investigate potential miRNA mechanisms, we performed a cross-sectional analysis using clinical data, dual-energy X-ray absorptiometry (DXA) scans, and miRNA and mRNA profiling of whole blood from the Framingham Study's Offspring Cohort. We found nine miRNAs associated with BB use and increased BMD. In parallel network analyses, we discovered a subnetwork associated with BMD and BB use containing two of these nine miRNAs, miR-19a-3p and miR-186-5p. To strengthen this finding, we showed that these two miRNAs had significantly higher expression in individuals without incident fracture compared with those with fracture in an external data set. We also noted a similar trend in association between these miRNA and Z-score as calculated from heel ultrasound measures in two external cohorts (SOS-Hip and SHIP-TREND). Because miR-19a directly targets the ADRB1 mRNA transcript, we propose BB use may downregulate ADRB1 expression in osteoblasts through increased miR-19a-3p expression. We used enrichment analysis of miRNA targets to find potential indirect effects through insulin and parathyroid hormone signaling. This analysis provides a starting point for delineating the role of miRNA on the association between BB use and BMD. © 2020 American Society for Bone and Mineral Research (ASBMR).
Identifiants
pubmed: 32786095
doi: 10.1002/jbmr.4160
pmc: PMC8140522
mid: NIHMS1652883
doi:
Substances chimiques
MIRN186 microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110-122Subventions
Organisme : NIGMS NIH HHS
ID : P30 GM106391
Pays : United States
Organisme : NIAMS NIH HHS
ID : K01 AR067858
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR041398
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM103392
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM115516
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM121301
Pays : United States
Informations de copyright
© 2020 American Society for Bone and Mineral Research (ASBMR).
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