Evidence for excessive osteoclast activation in SIRT6 null mice.
Evidence for excessive osteoclast activation in SIRT6 null mice.
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SIRT6 缺失小鼠中破骨细胞过度激活的证据
DOI：
10.1038/s41598-018-28716-z
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发表时间：
2018-07-20
影响因子：
4.6
通讯作者：
Zhou X
中科院分区：
文献类型：
--
作者：
Zhang D;Jing J;Lou F;Li R;Ping Y;Yu F;Wu F;Yang X;Xu R;Li F;Wang K;Bai M;Pi C;Xie J;Zheng L;Ye L;Zhou X
SIRT 6是NAD依赖性组蛋白3脱乙酰酶。据报道，SIRT 6缺失小鼠患有骨质减少。然而，SIRT 6在骨吸收中的作用仍不清楚。本研究主要探讨SIRT 6在破骨细胞中的作用。我们对突变小鼠的股骨、脊柱、牙槽骨甚至尾巴进行了组织学分析，发现突变小鼠的骨量急剧减少，而破骨细胞活性显著增加。这些表型通过TRAP染色和Pit吸收试验在细胞培养中的破骨细胞分化进一步证实。我们接下来发现突变破骨细胞前体的增殖活性增加，这可能是破骨细胞形成增强的原因。抗酒石酸酸性磷酸酶5 b的浓度，破骨细胞分化的标志物，是显着高于突变小鼠比对照组。破骨细胞生成相关基因和NF-κB信号相关基因表达显著上调。此外，成骨细胞/破骨细胞共培养实验表明，SIRT 6主要通过成骨细胞旁分泌的方式调控破骨细胞，而非破骨细胞自主行为。总之，SIRT 6基因敲除小鼠破骨细胞活化增强可能是通过NF-κB信号通路的过度活化和破骨细胞前体细胞增殖活性的增强，通过成骨细胞旁分泌方式在细胞水平上进行调节。
SIRT6 is a NAD-dependent histone 3 deacetylase. SIRT6 null mice have been reported suffering osteopenia. However, the role of SIRT6 in bone resorption is still not well understood. In this study, we focused on the role of SIRT6 in osteoclast. We performed histological analysis on the femur, spine, alveolar bone and even tail of mutant mice, and found the bone mass is sharply decreased while the osteoclast activity is significantly increased. These phenotypes were further demonstrated by the osteoclast differentiation in cell-cultures with TRAP staining and Pit Resorption Assay. We next found the proliferation activity of mutant osteoclast precursors was increased, which might account for the enhanced osteoclast formation. The concentration of tartrate-resistant acid phosphatase 5b, a marker of osteoclast differentiation, was significantly higher in the mutant mice than control. Besides, the osteoclastogenic and NF-κB signaling related genes were significantly up-regulated. Moreover, osteoblast/osteoclast co-culture demonstrated that SIRT6 regulated osteoclast mainly through osteoblast paracrine manner, rather than osteoclast-autonomous behavior. Together, the enhanced osteoclast activation in SIRT6 null mice might be regulated by the hyperactive NF-κB signaling and the enhanced proliferation activity of osteoclast precursors through osteoblast paracrine manner at the cellular level.
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影响因子：
4.1
作者：
Sugatani T;Agapova O;Malluche HH;Hruska KA
通讯作者：
Hruska KA
影响因子：
13.8
作者：
Kugel, Site;Mostoslavsky, Raul
通讯作者：
Mostoslavsky, Raul
影响因子：
4.6
作者：
Park SJ;Huh JE;Shin J;Park DR;Ko R;Jin GR;Seo DH;Kim HS;Shin HI;Oh GT;Kim HS;Lee SY
通讯作者：
Lee SY
影响因子：
4.1
作者：
Marcoline, Frank V.;Ishida, Yoichi;Mindell, Joseph A.;Nayak, Smita;Grabe, Michael
通讯作者：
Grabe, Michael
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影响因子：
4.6
作者：
Feng W;Liu H;Luo T;Liu D;Du J;Sun J;Wang W;Han X;Yang K;Guo J;Amizuka N;Li M
通讯作者：
Li M