LOXL3 Inhibits Autophagy of Chondrocytes by Activating Rheb in Osteoarthritis  

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作  者:Guang-ping ZHENG Chen LIU Liang ZHANG Qiang ZHONG Yun ZHANG Zhong-ming HUANG 

机构地区:[1]Ganzhou Municipal Key Laboratory of Bone and Joint Research,The Affiliated Ganzhou Hospital of Nanchang University,Ganzhou,341000,China [2]Research Center of Translational Medicine,Jinan Central Hospital Affiliated to Shandong First Medical University,Jinan,250013,China

出  处:《Current Medical Science》2023年第6期1195-1200,共6页当代医学科学(英文)

基  金:the National Natural Science Foundation of China(No.81702187);Natural Science Foundation of Jiangxi Province(No.20202BAB206019);Science Fund for Distinguished Young Scholars of Jiangxi Province(No.20224ACB216018);Scientific Talents Grants of Jiangxi Province(No.S2018LQCQ0800);Scientific Grants of Health Commission of Jiangxi Province(No.20194048);Scientific Innovation Talents Grants of Ganzhou(No.2019-60-08);Leading Talents Grants and Ph.D.Programs Foundation of Ganzhou People’s Hospital(No.Bsqd2019003)and Academic leaders Program of Ganzhou Institutes of Health.

摘  要:Objective This study aimed to investigate the potential mechanisms by which lysyl oxidase like 3(LOXL3)affects the autophagy in chondrocytes in osteoarthritis(OA),specifically through the activation of mammalian target of rapamycin complex 1(mTORC1).Methods To establish an OA model,rats underwent anterior cruciate ligament transection(ACLT).Chondrocytes were isolated from cartilage tissues and cultured.Western blotting was performed to assess the expression of LOXL3,Rheb,phosphorylation of p70S6K(p-p70S6K,a downstream marker of mTORC1),and autophagy markers.The autophagy of chondrocytes was observed using an immunofluorescence assay.Results The expression levels of both LOXL3 and Rheb proteins were upregulated in chondrocytes isolated from the OA model cartilage,in comparison to those from the normal cartilage.The silencing of LOXL3 resulted in a decrease in the protein levels of Rheb and p-p70S6K,as well as an increase in the expression of autophagy-related proteins.Additionally,the effect of LOXL3 could be reversed through the silencing of Rheb.The results of the immunofluorescence assay confirmed the impact of LOXL3 and Rheb on chondrocyte autophagy.Conclusion LOXL3 inhibits chondrocyte autophagy by activating the Rheb and mTORC1 signaling pathways.

关 键 词:OSTEOARTHRITIS LOXL3 RHEB mTORC1 CHONDROCYTE AUTOPHAGY 

分 类 号:R684.3[医药卫生—骨科学]

 

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