Reference - Detail
| RRC ID | 58150 |
|---|---|
| Author | 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 LF, Honda H, Shinohara M, Nagao M, Ogata T, Harada I, Sawada Y. |
| Title | Mechanical regulation of bone homeostasis through p130Cas-mediated alleviation of NF-κB activity. |
| Journal | Sci Adv |
| 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-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. |
| Volume | 5(9) |
| Pages | eaau7802 |
| Published | 2019-9-1 |
| DOI | 10.1126/sciadv.aau7802 |
| PII | aau7802 |
| PMID | 31579816 |
| PMC | PMC6760935 |
| MeSH | Animals Biomarkers Bone Resorption Bone and Bones / diagnostic imaging Bone and Bones / metabolism* Crk-Associated Substrate Protein / genetics Crk-Associated Substrate Protein / metabolism* Gene Expression Homeostasis* Mice Mice, Knockout NF-kappa B / metabolism* Osteoclasts / metabolism Osteocytes / metabolism RANK Ligand / genetics RANK Ligand / metabolism Signal Transduction* Stress, Mechanical* X-Ray Microtomography |
| IF | 13.117 |
| Times Cited | 4 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 9 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC02338 |