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- Title
Epigallocatechin‐3‐O‐gallate ameliorates oxidative stress‐induced chondrocyte dysfunction and exerts chondroprotective effects via the Keap1/Nrf2/ARE signaling pathway.
- Authors
Zhu, Wenrun; Tang, Han; Cao, Lu; Zhang, Jin; Li, Juncheng; Ma, Duan; Guo, Changan
- Abstract
Oxidative stress‐induced degeneration and dysfunction of chondrocytes play a key role in the pathological progression of osteoarthritis (OA), a common degenerative joint disease in the elderly. Epigallocatechin‐3‐O‐gallate (EGCG) increases Nrf2‐mediated antioxidase expression levels. We aimed to determine the effects of EGCG on C28/I2 human chondrocytes subjected to interleukin‐1β (IL‐1β)‐induced oxidative stress. EGCG suppressed IL‐1β‐induced oxidative stress, as indicated by decreased malondialdehyde (MDA) and reactive oxygen species (ROS) generation. Additionally, EGCG attenuated the IL‐1β‐induced reduction in cartilage matrix generated by chondrocytes by upregulating collagen II, aggrecan, sulfated proteoglycans, and SRY‐box transcription factor 9 (SOX9). EGCG reversed the IL‐1β‐induced increased cyclooxygenase 2 (COX2), inducible nitric oxide synthase (iNOS), collagen X, and matrix metalloproteinases (MMPs). Furthermore, EGCG inhibited apoptosis and senescence of IL‐1β‐treated chondrocytes, as indicated by the decrease in mitochondrial membrane potential and senescence‐associated β‐galactosidase‐positive cells, respectively. Mechanically, EGCG upregulated nuclear factor erythroid 2‐related factor 2 (Nrf2), oxygenase‐1 (HO‐1), and NADPH quinone oxidoreductase1 (NQO1). The antioxidant and chondroprotective effects of EGCG were blocked by ML385, a Keap1/Nrf2/ARE signaling pathway inhibitor. Thus, EGCG ameliorated oxidative stress‐induced chondrocyte dysfunction and exerted chondroprotective effects via Keap1/Nrf2/ARE signaling. This provides a novel perspective on the molecular mechanisms underlying the therapeutic effects of EGCG on OA.
- Subjects
CARTILAGE cells; NUCLEAR factor E2 related factor; SOX transcription factors; CELLULAR signal transduction; NITRIC-oxide synthases; OSTEOARTHRITIS
- Publication
Chemical Biology & Drug Design, 2022, Vol 100, Issue 1, p108
- ISSN
1747-0277
- Publication type
Article
- DOI
10.1111/cbdd.14056