KAT7 promotes chondrocyte senescence by activating the PI3K/AKT/mTOR signaling pathway
10.19405/j.cnki.issn1000-1492.2025.08.020
- VernacularTitle:KAT7 激活 PI3K/AKT/mTOR 信号通路促进软骨细胞衰老
- Author:
Kang Wang
1
;
Ying Li
1
;
Nuo Xu
1
;
Tingting Guo
2
;
Yun Chen
1
;
Xuran Zeng
1
;
Liqi Sun
1
;
Haochen Xu
1
;
Wei Wei
1
;
Shangxue Yan
3
Author Information
1. Institute of Clinical Pharmacology, Key Laboratory of Anti⁃inflammatory and Immune Medicine , Ministry of Education , Anhui Collaborative Innovation Center of Anti⁃inflammatory and Immune Drugs
2. Institute of Clinical Pharmacology, Key Laboratory of Anti⁃inflammatory and Immune Medicine , Ministry of Education , Anhui Collaborative Innovation Center of Anti⁃inflammatory and Immune Drugs Institute of Clinical Pharmacology, Key Laboratory of Anti⁃inflammatory and Immune Medicine , Ministry of Education , Anhui Collaborative Innovation Center of Anti⁃inflammatory and Immune Drugs
3. Institute of Clinical Pharmacology, Key Laboratory of Anti⁃inflammatory and Immune Medicine , Ministry of Education , Anhui Collaborative Innovation Center of Anti⁃inflammatory and Immune Drugs ; Laboratory Animal Center, Anhui Medical University, Hefei 230032
- Publication Type:Journal Article
- Keywords:
osteoarthritis;
articular chondrocytes;
KAT7;
cell senescence;
PI3K/AKT/mTOR
- From:
Acta Universitatis Medicinalis Anhui
2025;60(8):1506-1513
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To establish an interleukin-1β (Il-1β) induced inflammatory model of rat articular chondro- cytes (ACs) , and to investigate the relationship between the expression of lysine acetyltransferase 7 (KAT7) under inflammatory stimulation and the senescence of ACs.
Methods:Primary ACs were obtained by digestion of rat knee cartilage with collagenase type Ⅱ and identified. The inflammatory model of ACs was induced by IL-1β . KAT7 was over-expressed or knocked down in ACs by adeno-associated virus infection or small interfering RNA transfection , respectively. A negative control group was set up. Transwell assay was used to detect cell migration ability. Senes- cent cells were stained with senescence-associated β-galactosidase (SA-β-Gal) . Western blot ( WB) was used to detect the protein expression levels of KAT7 , collagen type II (Col Ⅱ ) , matrix metalloproteinase 13 (MMP13) , tumor protein p53 (p53) and cyclin-dependent kinase inhibitor 1A (p21) . The cells of negative control group and KAT7 over-expression group were performed for RNA sequencing , and WB was used to verify the related signaling pathways obtained by Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis.
Results:Compared with the control group , the SA-β-Gal staining was enhanced , the protein expression of Col Ⅱ decreased , the pro- tein expression of MMP13 and p53 increased , the cell migration ability decreased , and the expression of KAT7 also increased in the ACs of rats after IL-1β stimulation. Compared with the negative control group , the SA-β-Gal stai- ning was enhanced , the protein expression of Col Ⅱ decreased , the protein expression of MMP13 , p53 and p21 in- creased , and the cell migration ability decreased in the KAT7 over-expression group. Compared with the negative control group , the SA-β-Gal staining was weakened , the protein expression of Col Ⅱ increased , the protein expres- sion of MMP13 , p53 and p21 decreased , and the cell migration ability was enhanced in the KAT7 knockdown inflammatory model of ACs. KEGG enrichment analysis showed that phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was activated. Compared with the negative control group , the relative protein ex⁃pression levels of phosphorylated protein kinase B (p⁃AKT)/AKT and phosphorylated mammalian target of rapamy⁃cin (p⁃mTOR)/mTOR in KAT7 over⁃expression group increased. The relative protein expression levels of p ⁃AKT/AKT and p ⁃mTOR/mTOR in KAT7 knockdown cells decreased.
Conclusion:Rat ACs with high expression of KAT7 exhibit senescence and osteoarthritis phenotype , and the mechanism may be related to the activation of PI3K/AKT/mTOR signaling pathway by KAT7.
- Full text:2026041112210546770KAT7激活PI3K_AKT_mTOR信号通路促进软骨细胞衰老_王康.pdf
