Mechanical force promotes dimethylarginine dimethylaminohydrolase 1-mediated hydrolysis of the metabolite asymmetric dimethylarginine to enhance bone formation
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 osteoblas...
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Veröffentlicht in: | Nature communications 2022-01, Vol.13 (1), p.50-50, Article 50 |
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Sprache: | eng |
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Zusammenfassung: | 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.
Mechanical force is critical for the development and remodeling of bones. Here the authors report that mechanical force regulates the production of the metabolite asymmetric dimethylarginine via regulating the expression of the hydrolytic enzyme dimethylarginine dimethylaminohydrolase 1 in osteoblasts. |
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ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-021-27629-2 |