SIRT1 is a highly conserved type III acetyltransferase gene located on chromosome 10 in mammals that belong to the Sirtuins family. In order to explore the effects of the SIRT1 gene in the ATDC5 cell line, an RNAi SIRT1 target sequence was designed and synthesized, aimed to knockdown the expression of SIRT1 in ATDC5 by a lentivirus. Gene chip, qrt-PCR, and WES analyses were used to detect the expression of SIRT1 and changes to the Wnt signaling pathway, while detecting any changes in proliferation and differentiation factors. The results showed that the expressions of the SIRT1 gene, mRNA, and protein were lower after transfection of the RNAi SIRT1sequence into ATDC5 cells. The Wnt signaling pathway, especially the classical pathway, was inhibited by the knockdown of SIRT1. The cartilaginous proliferation and differentiation of ATDC5 cells were simultaneously inhibited, and apoptosis was accelerated. In summary, knocking down SIRT1 gene increased the degeneration of ATDC5 cells via inhibiting the Wnt signaling pathway. We also found some novel factors related to the Wnt signaling pathway after SIRT1 gene knockdown (BIRC3, IL1RAP, PPP3CA, PPP2R2A, PPP2R5E, GSN, PPP2R1B, etc), which might provide new clues in disease research related to chondrocyte degeneration.

中文翻译：

---

慢病毒介导的SIRT1基因敲低在ATDC5细胞系中的作用是通过抑制Wnt信号通路来实现的。

SIRT1是高度保守的III型乙酰基转移酶基因，位于Sirtuins家族的哺乳动物的10号染色体上。为了探索SIRT1基因在ATDC5细胞系中的作用，设计并合成了RNAi SIRT1目标序列，旨在通过慢病毒敲除SIDC1在ATDC5中的表达。基因芯片，qrt-PCR和WES分析用于检测SIRT1的表达和Wnt信号通路的变化，同时检测增殖和分化因子的任何变化。结果表明，将RNAi SIRT1序列转染至ATDC5细胞后，SIRT1基因，mRNA和蛋白质的表达降低。SIRT1的抑制可抑制Wnt信号通路，特别是经典通路。同时抑制ATDC5细胞的软骨增殖和分化，并促进细胞凋亡。总之，敲低SIRT1基因通过抑制Wnt信号通路增加了ATDC5细胞的变性。我们还发现了一些与SIRT1基因敲低后Wnt信号通路相关的新因素（BIRC3，IL1RAP，PPP3CA，PPP2R2A，PPP2R5E，GSN，PPP2R1B等），这可能为与软骨细胞变性相关的疾病研究提供新的线索。