Fibroblast growth factor 21 (FGF21) alleviates senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the SIRT1-mTOR signaling pathway
| Autor: | Jun Pan, Hongwei Lu, Haidong Jin, Zeng Lin, Chao Jia, Dengying Wu, Wei Wang, Xiucui Li |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Senescence Cancer Research Immunology Apoptosis Protective Agents Article Cellular and Molecular Neuroscience Chondrocytes Sirtuin 1 tert-Butylhydroperoxide Downregulation and upregulation Macroautophagy Matrix Metalloproteinase 13 Osteoarthritis Autophagy Animals Aggrecans Collagen Type II Cellular Senescence bcl-2-Associated X Protein QH573-671 Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Caspase 3 Chemistry TOR Serine-Threonine Kinases Cell Biology Extracellular Matrix Cell biology Fibroblast Growth Factors Mice Inbred C57BL Oxidative Stress TFEB Female ADAMTS5 Protein Signal transduction Cytology Flux (metabolism) Extracellular Matrix Degradation Signal Transduction |
| Zdroj: | Cell Death and Disease, Vol 12, Iss 10, Pp 1-13 (2021) Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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