論文

査読有り
2019年9月

Mechanical regulation of bone homeostasis through p130Cas-mediated alleviation of NF-κB activity

Science Advances
  • T. Miyazaki
  • ,
  • Z. Zhao
  • ,
  • Y. Ichihara
  • ,
  • D. Yoshino
  • ,
  • T. Imamura
  • ,
  • K. Sawada
  • ,
  • S. Hayano
  • ,
  • H. Kamioka
  • ,
  • S. Mori
  • ,
  • H. Hirata
  • ,
  • K. Araki
  • ,
  • K. Kawauchi
  • ,
  • K. Shigemoto
  • ,
  • S. Tanaka
  • ,
  • L. F. Bonewald
  • ,
  • H. Honda
  • ,
  • M. Shinohara
  • ,
  • M. Nagao
  • ,
  • T. Ogata
  • ,
  • I. Harada
  • ,
  • Y. Sawada

5
9
開始ページ
eaau7802
終了ページ
eaau7802
記述言語
掲載種別
研究論文(学術雑誌)
DOI
10.1126/sciadv.aau7802
出版者・発行元
American Association for the Advancement of Science (AAAS)

Mechanical loading plays an important role in bone homeostasis. However, molecular mechanisms behind the mechanical regulation of bone homeostasis are poorly understood. We previously reported p130Cas (Cas) as a key molecule in cellular mechanosensing at focal adhesions. Here, we demonstrate that Cas is distributed in the nucleus and supports mechanical loading–mediated bone homeostasis by alleviating NF-κB activity, which would otherwise prompt inflammatory processes. Mechanical unloading modulates Cas distribution and NF-κB activity in osteocytes, the mechanosensory cells in bones. Cas deficiency in osteocytes increases osteoclastic bone resorption associated with NF-κB–mediated RANKL expression, leading to osteopenia. Upon shear stress application on cultured osteocytes, Cas translocates into the nucleus and down-regulates NF-κB activity. Collectively, fluid shear stress–dependent Cas-mediated alleviation of NF-κB activity supports bone homeostasis. Given the ubiquitous expression of Cas and NF-κB together with systemic distribution of interstitial fluid, the Cas–NF-κB interplay may also underpin regulatory mechanisms in other tissues and organs.

リンク情報
DOI
https://doi.org/10.1126/sciadv.aau7802
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31579816
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760935
URL
https://syndication.highwire.org/content/doi/10.1126/sciadv.aau7802
ID情報
  • DOI : 10.1126/sciadv.aau7802
  • eISSN : 2375-2548
  • ORCIDのPut Code : 63818470
  • PubMed ID : 31579816
  • PubMed Central 記事ID : PMC6760935

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