Journal
JOURNAL OF CELL SCIENCE
Volume 125, Issue 9, Pages 2160-2171Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.096008
Keywords
RSK2; TNF-alpha; Osteopenia; TNF; Apoptosis; Osteoblast; Osteocyte
Categories
Funding
- Deutsche Forschungsgemeinschaft Interdisziplinares Zentrum fur Klinische Forschung Erlangen [A3]
- Deutsche Forschungsgemeinschaft [GK592, GK1660]
- Deutsche Forschungsgemeinschaft IMMUNOBONE [SPP1468]
- European Commission [2241719, 222509]
- Boehringer Ingelheim Stiftung
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available