Sirtuin 1 enzymatic activity is required for cartilage homeostasis in vivo in a mouse model.
Sirtuin 1 enzymatic activity is required for cartilage homeostasis in vivo in a mouse model.
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DOI：
10.1002/art.37750
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发表时间：
2013-01
影响因子：
--
通讯作者：
McBurney, Michael W.
中科院分区：
文献类型：
--
作者：
Gabay, Odile;Sanchez, Christelle;Dvir-Ginzberg, Mona;Gagarina, Viktoria;Zaal, Kristien J.;Song, Yingjie;He, Xiao Hong;McBurney, Michael W.
我们和其他人之前证明了sirtuin 1(SIRT-1)调节人类软骨细胞和小鼠模型中的软骨细胞凋亡和软骨特异性基因的表达。这项研究是通过研究SIRT-1突变小鼠的软骨特征来确定SIRT-1酶活性在体内软骨动态平衡中是否起到保护作用。从5个月和6个月大的野生型(WT)小鼠和SIRT-1tm2.1Mcby纯合子(SIRT-1Y/y)小鼠的爪子和膝盖获取关节软骨，SIRT-1Y/y是一种携带SIRT-1蛋白的点突变的等位基因，编码没有酶活性的SIRT-1蛋白(y/y小鼠)。同时对2日龄和6-7日龄小鼠进行检测。取小鼠关节软骨进行组织学检查或软骨细胞培养生化分析。我们发现，与来自WT小鼠的切片相比，来自6个月大的y/y小鼠的关节软骨组织切片含有较低水平的II型胶原、聚集素和糖胺聚糖。相反，在y/y小鼠的软骨中，基质金属蛋白酶8(MMP8)、MMP9和MMP13蛋白水平升高。此外，SIRT-1突变小鼠的软骨细胞凋亡率比它们的WT后代要高。与这些观察结果一致的是，蛋白酪氨酸磷酸酶1b在Y/Y小鼠中升高。我们在这个动物模型中的活体发现表明，SIRT-1缺陷的小鼠也有软骨缺陷，随着年龄的增长，软骨降解率上升。因此，正常的软骨动态平衡需要具有酶活性的SIRT-1蛋白。
We and others previously demonstrated that sirtuin 1 (SIRT-1) regulates apoptosis and cartilage-specific gene expression in human chondrocytes and mouse models. This study was undertaken to determine if SIRT-1 enzymatic activity plays a protective role in cartilage homeostasis in vivo, by investigating mice with SIRT-1 mutations to characterize their cartilage. Articular cartilage was harvested from the paws and knees of 5- and 6-month-old wild-type (WT) mice and mice homozygous for SIRT-1tm2.1Mcby (SIRT-1y/y), an allele carrying a point mutation that encodes a SIRT-1 protein with no enzymatic activity (y/y mice). Mice ages 2 days old and 6–7 days old were also examined. Mouse joint cartilage was processed for histologic examination or biochemical analyses of chondrocyte cultures. We found that articular cartilage tissue sections from y/y mice of up to 6 months of age contained reduced levels of type II collagen, aggrecan, and glycosaminoglycan compared to sections from WT mice. In contrast, protein levels of matrix metalloproteinase 8 (MMP-8), MMP-9, and MMP-13 were elevated in the cartilage of y/y mice. In addition, chondrocyte apoptosis was elevated in SIRT-1 mutant mice as compared to their WT littermates. Consistent with these observations, protein tyrosine phosphatase 1b was elevated in the y/y mice. Our in vivo findings in this animal model demonstrate that mice with defective SIRT-1 also have defective cartilage, with elevated rates of cartilage degradation with age. Hence, normal cartilage homeostasis requires enzymatically active SIRT-1 protein.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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