Ajugol's upregulation of TFEB-mediated autophagy alleviates endoplasmic reticulum stress in chondrocytes and retards osteoarthritis progression in a mouse model

Chinese Medicine

Research

Binghao Lin¹  Heng Yu¹  Zhao Zhang¹  Zhongke Lin¹  Jingtao Wu¹  Jiansen Miao¹  Yangcan Jin¹  Jingquan Wang¹  Teng Cheng¹  Liwen Zhou² 

[1] Department of Orthopaedics, Wenzhou Key Laboratory of Perinatal Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 325000, Wenzhou, Zhejiang Province, China;Key Laboratory of Orthopaedics of Zhejiang Province, 325000, Wenzhou, Zhejiang Province, China;The Second School of Medicine, Wenzhou Medical University, 325000, Wenzhou, Zhejiang Province, China;The First School of Medicine, Wenzhou Medical University, 325000, Wenzhou, Zhejiang Province, China;

关键词: Osteoarthritis;    Ajugol;    TBHP;    TFEB;    Autophagy;    ER stress;    DMM;   

DOI  :  10.1186/s13020-023-00824-7

 received in 2023-07-07, accepted in 2023-08-24,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundOsteoarthritis (OA), a degenerative disease with a high global prevalence, is characterized by the degradation of the extracellular matrix (ECM) and the apoptosis of chondrocytes. Ajugol, a extract derived from the herb Rehmannia glutinosa, has not yet been investigated for its potential in modulating the development of OA.MethodsWe employed techniques such as western blotting, immunofluorescence, immunohistochemistry, X-ray imaging, HE staining, and SO staining to provide biological evidence supporting the role of Ajugol as a potential therapeutic agent for modulating OA. Furthermore, in an in vivo experiment, intra-peritoneal injection of 50 mg/kg Ajugol effectively mitigated the progression of OA following destabilization of the medial meniscus (DMM) surgery.ResultsOur findings revealed that treatment with 50 μM Ajugol activated TFEB-mediated autophagy, alleviating ER stress-induced chondrocyte apoptosis and ECM degradation caused by TBHP. Furthermore, in an in vivo experiment, intra-peritoneal injection of 50 mg/kg Ajugol effectively mitigated the progression of OA following destabilization of the medial meniscus (DMM) surgery.ConclusionThese results provide compelling biological evidence supporting the role of Ajugol as a potential therapeutic agent for modulating OA by activating autophagy and attenuating ER stress-induced cell death and ECM degradation. The promising in vivo results further suggest the potential of Ajugol as a treatment strategy for OA progression.

【 授权许可】

CC BY   
© International Society for Chinese Medicine and BioMed Central Ltd. 2023

【 图 表 】

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