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Title: Mechanical regulation of bone homeostasis through p130Cas-mediated alleviation of NF-κB activity
Authors: Miyazaki, T.
Zhao, Z.
Ichihara, Y.
Yoshino, D.
Imamura, T.
Sawada, K.
Hayano, S.
Kamioka, H.
Mori, S.
Hirata, H. 
Araki, K. 
Kawauchi, K. 
Shigemoto, K.
Tanaka, S.
Bonewald, L.F.
Honda, H.
Shinohara, M.
Nagao, M.
Ogata, T.
Harada, I.
Sawada, Y. 
Issue Date: 2019
Publisher: American Association for the Advancement of Science
Citation: Miyazaki, T., Zhao, Z., Ichihara, Y., Yoshino, D., Imamura, T., Sawada, K., Hayano, S., Kamioka, H., Mori, S., Hirata, H., Araki, K., Kawauchi, K., Shigemoto, K., Tanaka, S., Bonewald, L.F., Honda, H., Shinohara, M., Nagao, M., Ogata, T., Harada, I., Sawada, Y. (2019). Mechanical regulation of bone homeostasis through p130Cas-mediated alleviation of NF-κB activity. Science Advances 5 (9) : eaau7802. ScholarBank@NUS Repository.
Rights: Attribution-NonCommercial 4.0 International
Abstract: 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-?B activity, which would otherwise prompt inflammatory processes. Mechanical unloading modulates Cas distribution and NF-?B activity in osteocytes, the mechanosensory cells in bones. Cas deficiency in osteocytes increases osteoclastic bone resorption associated with NF-?B–mediated RANKL expression, leading to osteopenia. Upon shear stress application on cultured osteocytes, Cas translocates into the nucleus and down-regulates NF-?B activity. Collectively, fluid shear stress–dependent Cas-mediated alleviation of NF-?B activity supports bone homeostasis. Given the ubiquitous expression of Cas and NF-?B together with systemic distribution of interstitial fluid, the Cas–NF-?B interplay may also underpin regulatory mechanisms in other tissues and organs. Copyright © 2019 The Authors.
Source Title: Science Advances
ISSN: 23752548
DOI: 10.1126/sciadv.aau7802
Rights: Attribution-NonCommercial 4.0 International
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