Antagonizing microRNA-19a/b augments PTH anabolic action and restores bone mass in osteoporosis in mice.
Tgif1
anti-miRNA
osteoporosis
parathyroid hormone
treatment
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
08 11 2022
08 11 2022
Historique:
revised:
12
09
2022
received:
20
10
2020
accepted:
13
09
2022
pubmed:
5
10
2022
medline:
10
11
2022
entrez:
4
10
2022
Statut:
ppublish
Résumé
Postmenopausal bone loss often leads to osteoporosis and fragility fractures. Bone mass can be increased by the first 34 amino acids of human parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrP), or by a monoclonal antibody against sclerostin (Scl-Ab). Here, we show that PTH and Scl-Ab reduce the expression of microRNA-19a and microRNA-19b (miR-19a/b) in bone. In bones from patients with lower bone mass and from osteoporotic mice, miR-19a/b expression is elevated, suggesting an inhibitory function in bone remodeling. Indeed, antagonizing miR-19a/b in vivo increased bone mass without overt cytotoxic effects. We identified TG-interacting factor 1 (Tgif1) as the target of miR-19a/b in osteoblasts and essential for the increase in bone mass following miR-19a/b inhibition. Furthermore, antagonizing miR-19a/b augments the gain in bone mass by PTH and restores bone loss in mouse models of osteoporosis in a dual mode of action by supporting bone formation and decreasing receptor activator of NF-κB ligand (RANKL)-dependent bone resorption. Thus, this study identifies novel mechanisms regulating bone remodeling, which opens opportunities for new therapeutic concepts to treat bone fragility.
Identifiants
pubmed: 36193848
doi: 10.15252/emmm.202013617
pmc: PMC9641424
doi:
Substances chimiques
MicroRNAs
0
TGIF1 protein, human
0
Repressor Proteins
0
Homeodomain Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13617Informations de copyright
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.
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