2. Academic Validation
  3. Fibroblast growth factor 21 (FGF21) alleviates senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the SIRT1-mTOR signaling pathway

Fibroblast growth factor 21 (FGF21) alleviates senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the SIRT1-mTOR signaling pathway

  • Cell Death Dis. 2021 Sep 23;12(10):865. doi: 10.1038/s41419-021-04157-x.
Hongwei Lu 1 2 3,  Chao Jia 1 2 3,  Dengying Wu 1 2 3,  Haidong Jin 1 2 3,  Zeng Lin 1 2 3,  Jun Pan 4 5 6,  Xiucui Li 7 8,  Wei Wang 9 10 11
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, Zhejiang Province, China.
  • 2 The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, China.
  • 3 Bone Research Institute, The Key Orthopaedic Laboratory of Zhejiang Province, Wenzhou, China.
  • 4 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, Zhejiang Province, China. [email protected].
  • 5 Bone Research Institute, The Key Orthopaedic Laboratory of Zhejiang Province, Wenzhou, China. [email protected].
  • 6 Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, China. [email protected].
  • 7 The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, China. [email protected].
  • 8 Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, China. [email protected].
  • 9 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, Zhejiang Province, China. [email protected].
  • 10 The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, China. [email protected].
  • 11 Bone Research Institute, The Key Orthopaedic Laboratory of Zhejiang Province, Wenzhou, China. [email protected].
PMID: 34556628 DOI: 10.1038/s41419-021-04157-x
Abstract

Osteoarthritis (OA) is a complex condition that involves both Apoptosis and senescence and currently cannot be cured. Fibroblast Growth Factor 21 (FGF21), known for its role as a potent regulator of glucose and energy metabolism, protects from various diseases, possibly by mediating Autophagy. In the present study, the role of FGF21 in the progression of OA was investigated in both in vitro and in vivo experiments. In vitro, the results revealed that FGF21 administration alleviated Apoptosis, senescence, and extracellular matrix (ECM) catabolism of the chondrocytes induced by tert-butyl hydroperoxide (TBHP) by mediating Autophagy flux. Furthermore, CQ, an Autophagy flux inhibitor, could reverse the protective effect of FGF21. It was observed that the FGF21-induced Autophagy flux enhancement was mediated by the nuclear translocation of TFEB, which occurs due to the activation of the SIRT1-mTOR signaling pathway. The in vivo experiments demonstrated that FGF21 treatment could reduce OA in the DMM model. Taken together, these findings suggest that FGF21 protects chondrocytes from Apoptosis, senescence, and ECM catabolism via Autophagy flux upregulation and also reduces OA development in vivo, demonstrating its potential as a therapeutic agent in OA.

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