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Mechanical force promotes dimethylarginine dimethylaminohydrolase 1-mediated hydrolysis of the metabolite asymmetric dimethylarginine to enhance bone formation

Author

Listed:
  • Ziang Xie

    (Zhejiang University School of Medicine
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

  • Lei Hou

    (Shanghai Jiaotong University School of Medicine)

  • Shuying Shen

    (Zhejiang University School of Medicine
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

  • Yizheng Wu

    (Zhejiang University School of Medicine
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

  • Jian Wang

    (Tongde Hospital of Zhejiang Province)

  • Zhiwei Jie

    (Zhejiang University School of Medicine
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

  • Xiangde Zhao

    (Zhejiang University School of Medicine
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

  • Xiang Li

    (Zhejiang University School of Medicine
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

  • Xuyang Zhang

    (Zhejiang University School of Medicine
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

  • Junxin Chen

    (Zhejiang University School of Medicine
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

  • Wenbin Xu

    (Zhejiang University School of Medicine
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

  • Lei Ning

    (Zhejiang University School of Medicine
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

  • Qingliang Ma

    (Zhejiang University School of Medicine
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

  • Shiyu Wang

    (Zhejiang University School of Medicine
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

  • Haoming Wang

    (Zhejiang University School of Medicine
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

  • Putao Yuan

    (Zhejiang University School of Medicine
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

  • Xiangqian Fang

    (Zhejiang University School of Medicine
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

  • An Qin

    (Shanghai Jiaotong University School of Medicine)

  • Shunwu Fan

    (Zhejiang University School of Medicine
    Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province)

Abstract

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.

Suggested Citation

  • Ziang Xie & Lei Hou & Shuying Shen & Yizheng Wu & Jian Wang & Zhiwei Jie & Xiangde Zhao & Xiang Li & Xuyang Zhang & Junxin Chen & Wenbin Xu & Lei Ning & Qingliang Ma & Shiyu Wang & Haoming Wang & Puta, 2022. "Mechanical force promotes dimethylarginine dimethylaminohydrolase 1-mediated hydrolysis of the metabolite asymmetric dimethylarginine to enhance bone formation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27629-2
    DOI: 10.1038/s41467-021-27629-2
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