title: RSK2 protects mice against TNF-induced bone loss.
abstract: Tumor necrosis factor (TNF)-α is a key cytokine regulator of bone and mediates inflammatory bone loss. The molecular signaling that regulates bone loss downstream of TNF-α 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-α [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.affiliation: Internal Medicine 3, Rheumatology and Immunology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Böhm
authors.forename: Anja
authors.initials: A
authors.lastname: Derer
authors.forename: Roland
authors.initials: R
authors.lastname: Axmann
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hillienhoff
authors.forename: Mario M
authors.initials: MM
authors.lastname: Zaiss
authors.forename: Julia
authors.initials: J
authors.lastname: Luther
authors.forename: Christine
authors.initials: C
authors.lastname: Zech
authors.forename: Michael
authors.initials: M
authors.lastname: Stock
authors.forename: Carina
authors.initials: C
authors.lastname: Scholtysek
authors.forename: Klaus
authors.initials: K
authors.lastname: Engelke
authors.forename: Andreas
authors.initials: A
authors.lastname: Hess
authors.forename: Jan P
authors.initials: JP
authors.lastname: Tuckermann
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: David
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3