Osteoblast lineage Sod2 deficiency leads to an osteoporosis-like phenotype in mice.
Mitochondrial dysfunction
Osteoporosis
Reactive oxygen species
Senescence
Skeletal aging
Journal
Disease models & mechanisms
ISSN: 1754-8411
Titre abrégé: Dis Model Mech
Pays: England
ID NLM: 101483332
Informations de publication
Date de publication:
01 05 2022
01 05 2022
Historique:
received:
10
11
2021
accepted:
25
03
2022
pubmed:
9
4
2022
medline:
18
5
2022
entrez:
8
4
2022
Statut:
ppublish
Résumé
Osteoporosis is a systemic metabolic skeletal disease characterized by low bone mass and strength associated with fragility fractures. Oxidative stress, which results from elevated intracellular reactive oxygen species (ROS) and arises in the aging organism, is considered one of the critical factors contributing to osteoporosis. Mitochondrial (mt)ROS, as the superoxide anion (O2-) generated during mitochondrial respiration, are eliminated in the young organism by antioxidant defense mechanisms, including superoxide dismutase 2 (SOD2), the expression and activity of which are decreased in aging mesenchymal progenitor cells, accompanied by increased mtROS production. Using a mouse model of osteoblast lineage cells with Sod2 deficiency, we observed significant bone loss in trabecular and cortical bones accompanied by decreased osteoblast activity, increased adipocyte accumulation in the bone marrow and augmented osteoclast activity, suggestive of altered mesenchymal progenitor cell differentiation and osteoclastogenesis. Furthermore, osteoblast senescence was increased. To date, there are only a few studies suggesting a causal association between mtROS and cellular senescence in tissue in vivo. Targeting SOD2 to improve redox homeostasis could represent a potential therapeutic strategy for maintaining bone health during aging.
Identifiants
pubmed: 35394023
pii: 274992
doi: 10.1242/dmm.049392
pmc: PMC9118037
pii:
doi:
Substances chimiques
Reactive Oxygen Species
0
Superoxide Dismutase
EC 1.15.1.1
superoxide dismutase 2
EC 1.15.1.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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