Sirt6 regulates postnatal growth plate differentiation and proliferation via Ihh signaling.
Sirt6 regulates postnatal growth plate differentiation and proliferation via Ihh signaling.
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SIRT6通过IHH信号传导调节产后生长板的分化和增殖。
DOI：
10.1038/srep03022
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发表时间：
2013-10-23
影响因子：
4.6
通讯作者：
Asou Y
中科院分区：
文献类型：
--
作者：
Piao J;Tsuji K;Ochi H;Iwata M;Koga D;Okawa A;Morita S;Takeda S;Asou Y
Sirtuin 6（Sirt 6）是NAD+依赖性组蛋白去乙酰化酶Sir 2的哺乳动物同源物。虽然Sirt 6 −/−小鼠表现出生长迟缓，但Sirt 6在软骨代谢中的作用尚不清楚。本研究旨在探讨Sirt 6信号通路在软骨代谢中的作用。Sirt 6 −/−小鼠胫骨生长板的免疫组织学评价显示软骨细胞增殖和分化受损，印度刺猬（Ihh）表达减少，以及衰老表型。当Sirt 6在体外软骨细胞中被敲低时，Ihh及其下游基因的表达降低。通过施用Hh信号激动剂完全挽救了由Sirt 6沉默引起的分化受损。当sirtuins被激活时，软骨细胞分化与Ihh信号的激活一起增强，并且这些效果被Sirt 6沉默所废除。ChIP分析显示，ATF 4与Ihh启动子的亲和力被Sirt 6敲低显著降低。这些数据表明Sirt 6直接控制软骨细胞的增殖和分化。
Sirtuin 6 (Sirt6) is a mammalian homologue of NAD+-dependent histone deacetylase Sir2. Although Sirt6−/− mice exhibit growth retardation, the role of Sirt6 in cartilage metabolism is unclear. The aim of this study was to investigate the Sirt6 signaling pathway in cartilage metabolism. Immunohistological evaluation of the tibial growth plate in Sirt6−/− mice exhibited impaired proliferation and differentiation of chondrocytes, reduced expression of Indian hedgehog (Ihh), and a senescent phenotype. When Sirt6 was knocked down in chondrocytes in vitro, expression of Ihh and its downstream genes were reduced. Impaired differentiation by Sirt6 silencing was completely rescued by administration of a Hh signal agonist. When sirtuins were activated, chondrocyte differentiation was enhanced together with activation of Ihh signal, and these effects were abrogated by Sirt6 silencing. ChIP assay revealed the affinity of ATF4 to the Ihh promoter was markedly decreased by Sirt6 knockdown. These data indicate Sirt6 directly controls proliferation and differentiation of chondrocytes.
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影响因子：
10.5
作者：
POWELLBRAXTON, L;HOLLINGSHEAD, P;STEWART, TA
通讯作者：
STEWART, TA
神经沉默调节蛋白 6 (Sirt6) 消融会减弱体细胞生长并导致肥胖
DOI：
10.1073/pnas.1016306107
发表时间：
2010-12-14
影响因子：
11.1
作者：
Schwer, Bjoern;Schumacher, Bjoern;Alt, Frederick W.
通讯作者：
Alt, Frederick W.
影响因子：
64.5
作者：
Kawahara TL;Michishita E;Adler AS;Damian M;Berber E;Lin M;McCord RA;Ongaigui KC;Boxer LD;Chang HY;Chua KF
通讯作者：
Chua KF
影响因子：
4.8
作者：
Sharma, Amit;Diecke, Sebastian;Wu, Joseph C.
通讯作者：
Wu, Joseph C.
影响因子：
4.6
作者：
Mak, Kinglun Kingston;Kronenberg, Henry M.;Yang, Yingzi
通讯作者：
Yang, Yingzi