Mechanical force promotes dimethylarginine dimethylaminohydrolase 1-mediated hydrolysis of the metabolite asymmetric dimethylarginine to enhance bone formation.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 01 2022
10 01 2022
Historique:
received:
20
09
2020
accepted:
30
11
2021
entrez:
11
1
2022
pubmed:
12
1
2022
medline:
28
1
2022
Statut:
epublish
Résumé
Mechanical force is critical for the development and remodeling of bone. Here we report that mechanical force regulates the production of the metabolite asymmetric dimethylarginine (ADMA) via regulating the hydrolytic enzyme dimethylarginine dimethylaminohydrolase 1 (Ddah1) expression in osteoblasts. The presence of -394 4 N del/ins polymorphism of Ddah1 and higher serum ADMA concentration are negatively associated with bone mineral density. Global or osteoblast-specific deletion of Ddah1 leads to increased ADMA level but reduced bone formation. Further molecular study unveils that mechanical stimulation enhances TAZ/SMAD4-induced Ddah1 transcription. Deletion of Ddah1 in osteoblast-lineage cells fails to respond to mechanical stimulus-associated bone formation. Taken together, the study reveals mechanical force is capable of down-regulating ADMA to enhance bone formation.
Identifiants
pubmed: 35013196
doi: 10.1038/s41467-021-27629-2
pii: 10.1038/s41467-021-27629-2
pmc: PMC8748781
doi:
Substances chimiques
N,N-dimethylarginine
63CV1GEK3Y
Arginine
94ZLA3W45F
Amidohydrolases
EC 3.5.-
dimethylargininase
EC 3.5.3.18
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
50Informations de copyright
© 2022. The Author(s).
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