CREB Ameliorates Osteoarthritis Progression Through Regulating Chondrocytes Autophagy
CREB
METTL3
autophagy
miR-373
osteoarthritis
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2021
2021
Historique:
received:
17
09
2021
accepted:
23
12
2021
entrez:
27
6
2022
pubmed:
28
6
2022
medline:
28
6
2022
Statut:
epublish
Résumé
Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation. Dysregulated autophagy is a major cause of OA. However, the underlying mechanism is unclear. Here, we found that the expression of element-binding protein (CREB) was downregulated in both cartilage tissues of OA patients and mouse OA model. In tert-butyl hydroperoxide solution-treated chondrocytes, increased apoptosis and autophagic blockage were attenuated by CREB overexpression. Mechanically, MiR-373 directly targeted the 3'UTR of methyltransferase-like 3 (METTL3) and led to its downregulation. METTL3 epigenetically suppressed TFEB. The upregulation of miR-373 by CREB overexpression induced the release of TFEB from METTL3 and restored the autophagy activity of chondrocytes. Taken together, our study showed that CREB alleviates OA injury through regulating the expression of miR-373, which directly targeted METTL3, and finally relieved TFEB from METTL3-mediated epigenetic suppression. The CREB/miR-373/METTL3/TFEB axis may be used as a potential target for the treatment of OA.
Identifiants
pubmed: 35756079
doi: 10.3389/fcell.2021.778941
pii: 778941
pmc: PMC9218638
doi:
Types de publication
Journal Article
Langues
eng
Pagination
778941Informations de copyright
Copyright © 2022 Zhang, Li, Li, Yang, Liao, Wang and Yang.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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