军事医学2024，Vol.48Issue(8)：579-585,7.DOI:10.7644/j.issn.1674-9960.2024.08.004
Sestrin2通过调控mTORC1通路在骨性关节炎中的保护机制研究
Sestrin2 protects against osteoarthritis by regulating the mTORC1 pathway
摘要
Abstract
Objective To explore the mechanism by which Sestrin2(SESN2)regulates autophagy activity of chondrocytes by mediating mammalian rapamycin target protein complex 1(mTORC1)signaling pathway.Methods The normal chondrocytes were treated with interleukin-1 β(IL-1β)to establish an osteoarthritis(OA)chondrocyte model,which was divided into the control group and the IL-1 β-treated group.Real-time quantitative PCR(qPCR)and Western blot were used to detect the expression levels of matrix metalloproteinase 13(MMP13),type Ⅱ collagen(COL2A1)and SESN2 in the two groups.The cell models of the chondrocyte overexpression SESN2 group and knockdown SESN2 group were obtained via cell transfection technology,and the expression levels of SESN2 in each group were detected by qPCR while those of SESN2,MMP13,COL2A1,mTORC1 pathway-related proteins and autophagy-related proteins in each group were detected by Western blot.The effects of SESN2 on cell proliferation and migration were detected by CCK-8 and cell scratch assay.Results(1)The expression level of MMP13 in the IL-1 β-treated group was significantly up-regulated,while the expression levels of COL2A1 and SESN2 were significantly decreased.(2)Compared with the control group,the expressions of p-mTORC1,ribosomal protein S6 kinase 1(S6K1),and MMP13 protein in OA chondrocytes in the overexpression group were significantly down-regulated,while the expressions of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)and chondroprotective gene COL2A1 were significantly increased,and the expression level of Beclin-1 and the ratio of microtubule associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)/(LC3-Ⅰ)were increased.Meanwhile,overexpression of SESN2 could up-regulate the proliferation and migration of chondrocytes,but the results were opposite after knockdown of SESN2.Conclusion SESN2 can enhance autophagy,proliferation and migration of chondrocytes by inhibiting mTORC1 pathway,which has provided data for revealing the pathogenesis of OA and exploring new therapeutic methods.关键词
骨性关节炎/软骨细胞/Sestrin2/mTORC1/自噬/细胞增殖/细胞迁移Key words
osteoarthritis/chondrocyte/sestrin2/mTORC1/autophagy/cell proliferation/cell migration分类
医药卫生引用本文复制引用
刘泽众,李彩霞,刘晓光,付道通,刘长杰,张益民,赵世波..Sestrin2通过调控mTORC1通路在骨性关节炎中的保护机制研究[J].军事医学,2024,48(8):579-585,7.基金项目
山东省医药卫生科技发展计划项目(202104070723) （202104070723）
山东省自然科学基金课题面上项目(ZR2020MH094) （ZR2020MH094）
山东省自然科学基金青年基金项目(ZR2019PH026) （ZR2019PH026）
潍坊市卫健委科研计划项目(WFWSJK-2022-057) （WFWSJK-2022-057）
金天格中青年科研培养基金 （）
