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

  • Chin Med. 2023 Sep 7;18(1):113. doi: 10.1186/s13020-023-00824-7.
Jingtao Wu  1  2  3 ,  Heng Yu  1  2  3 ,  Yangcan Jin  1  2  3 ,  Jingquan Wang  1  2  3 ,  Liwen Zhou  4 ,  Teng Cheng  1  2  3 ,  Zhao Zhang  1  2  3 ,  Binghao Lin  1  2  3 ,  Jiansen Miao  1  2  3 ,  Zhongke Lin  5  6  7
Affiliations
  • 1. Department of Orthopaedics, Wenzhou Key Laboratory of Perinatal Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
  • 2. Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, 325000, Zhejiang Province, China.
  • 3. The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
  • 4. The First School of Medicine, Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
  • 5. Department of Orthopaedics, Wenzhou Key Laboratory of Perinatal Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China. [email protected].
  • 6. Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, 325000, Zhejiang Province, China. [email protected].
  • 7. The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China. [email protected].
PMID: 37679844 DOI: 10.1186/s13020-023-00824-7
Abstract

Background: Osteoarthritis (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.

Methods: We 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.

Results: Our 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.

Conclusion: These 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.

Keywords
Ajugol; Autophagy; DMM; ER stress; Osteoarthritis; TBHP; TFEB.
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