Magnesium implantation or supplementation ameliorates bone disorder in CFTR-mutant mice through an ATF4-dependent Wnt/β-catenin signaling.
ATF4
Cystic fibrosis-related bone disorder
Magnesium implant
Wnt/β-catenin signaling
Journal
Bioactive materials
ISSN: 2452-199X
Titre abrégé: Bioact Mater
Pays: China
ID NLM: 101685294
Informations de publication
Date de publication:
Feb 2022
Feb 2022
Historique:
received:
11
04
2021
revised:
26
06
2021
accepted:
27
06
2021
entrez:
20
9
2021
pubmed:
21
9
2021
medline:
21
9
2021
Statut:
epublish
Résumé
Magnesium metal and its alloys are being developed as effective orthopedic implants; however, the mechanisms underlying the actions of magnesium on bones remain unclear. Cystic fibrosis, the most common genetic disease in Caucasians caused by the mutation of CFTR, has shown bone disorder as a key clinical manifestation, which currently lacks effective therapeutic options. Here we report that implantation of magnesium-containing implant stimulates bone formation and improves bone fracture healing in CFTR-mutant mice. Wnt/β-catenin signaling in the bone is enhanced by the magnesium implant, and inhibition of Wnt/β-catenin by iCRT14 blocks the magnesium implant to improve fracture healing in CFTR-mutant mice. We further demonstrate that magnesium ion enters osteocytes, increases intracellular cAMP level and activates ATF4, a key transcription factor known to regulate Wnt/β-catenin signaling.
Identifiants
pubmed: 34541389
doi: 10.1016/j.bioactmat.2021.06.034
pii: S2452-199X(21)00320-0
pmc: PMC8424424
doi:
Types de publication
Journal Article
Langues
eng
Pagination
95-108Informations de copyright
© 2021 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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