2. Academic Validation
  3. 20-Deoxyingenol alleviates osteoarthritis by activating TFEB in chondrocytes

20-Deoxyingenol alleviates osteoarthritis by activating TFEB in chondrocytes

  • Pharmacol Res. 2021 Mar;165:105361. doi: 10.1016/j.phrs.2020.105361.
Mingbao Gu 1,  Jie Jin 1,  Chenghao Ren 1,  Ximiao Chen 2,  Zongyou Pan 3,  Yaosen Wu 1,  Naifeng Tian 1,  Liaojun Sun 1,  Aimin Wu 1,  Weiyang Gao 1,  Yifei Zhou 4,  Zhongke Lin 5,  Xiaolei Zhang 6
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  • 2 Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, Zhejiang Province, China; Department of Orthopaedics, Affiliated Hospital of Guilin Medical College, Guilin, Guangxi Province, China.
  • 3 Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
  • 4 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. Electronic address: [email protected].
  • 5 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. Electronic address: [email protected].
  • 6 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Chinese Orthopaedic Regenerative Medicine Society, Hangzhou, Zhejiang Province, China. Electronic address: [email protected].
PMID: 33460793 DOI: 10.1016/j.phrs.2020.105361
Abstract

Osteoarthritis (OA) is an age-related degenerative disease and currently cannot be cured. Transcription factor EB (TFEB) is one of the major transcriptional factors that regulates Autophagy and lysosomal biogenesis. TFEB has been shown to be an effective therapeutic target for many diseases including OA. The current study explores the therapeutic effects of 20-Deoxyingenol (20-DOI) on OA as well as its working mechanism on TFEB regulation. The in vitro study showed that 20-DOI may suppress Apoptosis and senescence induced by oxidative stress in chondrocytes; it may also promote the nuclear localization of TFEB in chondrocytes. Knock-down of TFEB compromised the effects of 20-DOI on Apoptosis and senescence. The in vivo study demonstrated that 20-DOI may postpone the progression of OA in mouse destabilization of the medial meniscus (DMM) model; it may also suppress Apoptosis and senescence and promote the nuclear localization of TFEB in chondrocytes in vivo. This work suggests that 20-Deoxyingenol may alleviate osteoarthritis by activating TFEB in chondrocytes, while 20-DOI may become a potential drug for OA therapy.

Keywords

20-Deoxyingenol; 4′,6-Diamidino-2-phenylindole(DAPI); Autophagy; Ethanol; Hematoxylin and eosin; Hydrogen peroxide; Lysosomal biogenesis; Osteoarthritis; Paraformaldehyde; Penicillin/streptomycin; Safranin O and fast green; Sodium pentobarbital; TFEB; Tert-butyl hydroperoxide solution (TBHP); Triton X-100; Xylene.

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