| First Author | Böhm C | Year | 2012 |
| Journal | J Cell Sci | Volume | 125 |
| Issue | Pt 9 | Pages | 2160-71 |
| PubMed ID | 22344264 | Mgi Jnum | J:197283 |
| Mgi Id | MGI:5492004 | Doi | 10.1242/jcs.096008 |
| Citation | Bohm C, et al. (2012) RSK2 protects mice against TNF-induced bone loss. J Cell Sci 125(Pt 9):2160-71 |
| abstractText | Tumor necrosis factor (TNF)-alpha is a key cytokine regulator of bone and mediates inflammatory bone loss. The molecular signaling that regulates bone loss downstream of TNF-alpha is poorly defined. Here, we demonstrate that inactivating the pro-osteoblastogenic ERK-activated ribosomal S6 kinase RSK2 leads to a drastically accelerated and amplified systemic bone loss in mice ectopically expressing TNF-alpha [human TNF transgenic (hTNFtg) mice]. The phenotype is associated with a decrease in bone formation because of fewer osteoblasts as well as a drastically increased bone destruction by osteoclasts. The molecular basis of this phenotype is a cell autonomous increased sensitivity of osteoblasts and osteocytes to TNF-induced apoptosis combined with an enhancement of their osteoclast supportive activity. Thus, RSK2 exerts a strong negative regulatory loop on TNF-induced bone loss. |
