| First Author | Miyazaki T | Year | 2019 |
| Journal | Sci Adv | Volume | 5 |
| Issue | 9 | Pages | eaau7802 |
| PubMed ID | 31579816 | Mgi Jnum | J:287570 |
| Mgi Id | MGI:6415857 | Doi | 10.1126/sciadv.aau7802 |
| Citation | Miyazaki T, et al. (2019) Mechanical regulation of bone homeostasis through p130Cas-mediated alleviation of NF-kappaB activity. Sci Adv 5(9):eaau7802 |
| abstractText | 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-kappaB activity, which would otherwise prompt inflammatory processes. Mechanical unloading modulates Cas distribution and NF-kappaB activity in osteocytes, the mechanosensory cells in bones. Cas deficiency in osteocytes increases osteoclastic bone resorption associated with NF-kappaB-mediated RANKL expression, leading to osteopenia. Upon shear stress application on cultured osteocytes, Cas translocates into the nucleus and down-regulates NF-kappaB activity. Collectively, fluid shear stress-dependent Cas-mediated alleviation of NF-kappaB activity supports bone homeostasis. Given the ubiquitous expression of Cas and NF-kappaB together with systemic distribution of interstitial fluid, the Cas-NF-kappaB interplay may also underpin regulatory mechanisms in other tissues and organs. |
