RSK2 protects mice against TNF-induced bone loss
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RSK2 protects mice against TNF-induced bone loss. / Böhm, Christina; Derer, Anja; Axmann, Roland; Hillienhoff, Ulrike; Zaiss, Mario M; Luther, Julia; Zech, Christine; Stock, Michael; Scholtysek, Carina; Engelke, Klaus; Hess, Andreas; Tuckermann, Jan P; Schett, Georg; David, Jean-Pierre.
In: J CELL SCI, Vol. 125, No. Pt 9, 01.05.2012, p. 2160-71.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - RSK2 protects mice against TNF-induced bone loss
AU - Böhm, Christina
AU - Derer, Anja
AU - Axmann, Roland
AU - Hillienhoff, Ulrike
AU - Zaiss, Mario M
AU - Luther, Julia
AU - Zech, Christine
AU - Stock, Michael
AU - Scholtysek, Carina
AU - Engelke, Klaus
AU - Hess, Andreas
AU - Tuckermann, Jan P
AU - Schett, Georg
AU - David, Jean-Pierre
PY - 2012/5/1
Y1 - 2012/5/1
N2 - 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.
AB - 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.
KW - Animals
KW - Apoptosis
KW - Bone Resorption
KW - Bone and Bones
KW - Gene Expression
KW - Humans
KW - Male
KW - Mice
KW - Mice, Transgenic
KW - Osteoblasts
KW - Osteoclasts
KW - Ribosomal Protein S6 Kinases, 90-kDa
KW - Signal Transduction
KW - Tumor Necrosis Factor-alpha
U2 - 10.1242/jcs.096008
DO - 10.1242/jcs.096008
M3 - SCORING: Journal article
C2 - 22344264
VL - 125
SP - 2160
EP - 2171
JO - J CELL SCI
JF - J CELL SCI
SN - 0021-9533
IS - Pt 9
ER -