NRF2 function in osteocytes is required for bone homeostasis and drives osteocytic gene expression.
Bone
Bone homeostasis
NRF2
Osteocyte
Osteoporosis
Oxidative stress
Journal
Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
30
11
2020
accepted:
21
12
2020
pubmed:
30
12
2020
medline:
22
6
2021
entrez:
29
12
2020
Statut:
ppublish
Résumé
Osteocytes, the most abundant bone cell type, are derived from osteoblasts through a process in which they are embedded in an osteoid. We previously showed that nutrient restriction promotes the osteocyte transcriptional program and is associated with increased mitochondrial biogenesis. Here, we show that increased mitochondrial biogenesis increase reactive oxygen species (ROS) levels and consequently, NRF2 activity during osteocytogenesis. NRF2 activity promotes osteocyte-specific expression of Dmp1, Mepe, and Sost in IDG-SW3 cells, primary osteocytes, and osteoblasts, and in murine models with Nfe2l2 deficiency in osteocytes or osteoblasts. Moreover, ablation of Nfe2l2 in osteocytes or osteoblasts generates osteopenia and increases osteoclast numbers with marked sexual dimorphism. Finally, treatment with dimethyl fumarate prevented the deleterious effects of ovariectomy in trabecular bone masses of mice and restored osteocytic gene expression. Altogether, we uncovered the role of NRF2 activity in osteocytes during the regulation of osteocyte gene expression and maintenance of bone homeostasis.
Identifiants
pubmed: 33373776
pii: S2213-2317(20)31050-8
doi: 10.1016/j.redox.2020.101845
pmc: PMC7773566
pii:
doi:
Substances chimiques
NF-E2-Related Factor 2
0
Nfe2l2 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101845Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.