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Silent information regulator (Sir)T1 inhibits NF-κB signaling to maintain normal skeletal remodeling.
Edwards, James R; Perrien, Daniel S; Fleming, Nicole; Nyman, Jeffry S; Ono, Koichiro; Connelly, Linda; Moore, Megan M; Lwin, Seint T; Yull, Fiona E; Mundy, Gregory R; Elefteriou, Florent.
Afiliação
  • Edwards JR; Vanderbilt Center for Bone Biology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA. James.Edwards@ndorms.ox.ac.uk
J Bone Miner Res ; 28(4): 960-9, 2013 Apr.
Article em En | MEDLINE | ID: mdl-23172686
Silent information regulator T1 (SirT1) is linked to longevity and negatively controls NF-κB signaling, a crucial mediator of survival and regulator of both osteoclasts and osteoblasts. Here we show that NF-κB repression by SirT1 in both osteoclasts and osteoblasts is necessary for proper bone remodeling and may contribute to the mechanisms linking aging and bone loss. Osteoclast- or osteoblast-specific SirT1 deletion using the Sirt(flox/flox) mice crossed to lysozyme M-cre and the 2.3 kb col1a1-cre transgenic mice, respectively, resulted in decreased bone mass caused by increased resorption and reduced bone formation. In osteoclasts, lack of SirT1 promoted osteoclastogenesis in vitro and activated NF-κB by increasing acetylation of Lysine 310. Importantly, this increase in osteoclastogenesis was blocked by pharmacological inhibition of NF-κB. In osteoblasts, decreased SirT1 reduced osteoblast differentiation, which could also be rescued by inhibition of NF-κB. In further support of the critical role of NF-κB signaling in bone remodeling, elevated NF-κB activity in IκBα(+/-) mice uncoupled bone resorption and formation, leading to reduced bone mass. These findings support the notion that SirT1 is a genetic determinant of bone mass, acting in a cell-autonomous manner in both osteoblasts and osteoclasts, through control of NF-κB and bone cell differentiation.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / NF-kappa B / Remodelação Óssea / Sirtuína 1 Limite: Animals Idioma: En Revista: J Bone Miner Res Assunto da revista: METABOLISMO / ORTOPEDIA Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / NF-kappa B / Remodelação Óssea / Sirtuína 1 Limite: Animals Idioma: En Revista: J Bone Miner Res Assunto da revista: METABOLISMO / ORTOPEDIA Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos