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Peroxiredoxin 4 inhibits IL-1β-induced chondrocyte apoptosis via PI3K/AKT signaling
Zhitao Rao1, Shuqing Wang1, Jiaqi Wang1
1Department of Orthopaedics, Tongji Hospital, Tongji University School of Medicine, Shanghai, 20065, China.
Background:
Chondrocytes apoptosis induced by reactive oxygen species (ROS) plays a critical role in the pathogenesis of osteoarthritis (OA). Peroxiredoxin 4 (PRDX4), a member of the PRDX family, is essential for removing metabolic free radicals and reducing intracellular ROS. In this study, we sought to investigate the roles of PRDX4 on interleukin 1β (IL-1β)-induced chondrocyte apoptosis.
Methods:
Primary chondrocytes were isolated from the articular cartilage of Sprague-Dawley rats, infected with PRDX4 overexpressing lentivirus and treated with IL-1β (10ng/mL). Cell apoptosis and ROS production identified by flow cytometry. Protein expression levels was evaluated by Western blotting analysis. Nitric oxide (NO) production and Caspase-3/9 activation were assessed by the Griess reaction method and colorimetric assay kit, respectively.
Results:
PRDX4 overexpression in chondrocytes significantly decreased IL-1β-induced apoptosis. It also reversed the activity of IL-1β that increased ROS and NO production. PRDX4 overexpression reversed the activity of IL-1β that reduced the levels of Bcl-2, p-AKT and p-PRAS40, as well as increased Bax levels and Caspase-3/9 activation. More importantly, pre-treated with AKT inhibitor (AZD5363) significantly reduced the protective effects of PRDX4.
Conclusions:
Our data demonstrated that the regulatory effects of PRDX4 on IL-1β-induced chondrocyte apoptosis can be partially attributed to phosphatidylinositol 3-kinase/AKT signaling. These results indicate that PRDX4 might play a protective role in OA cartilage degeneration.
Insights
Peroxiredoxin 4 (PRDX4) protects against osteoarthritis by reducing reactive oxygen species (ROS) and preventing chondrocyte apoptosis. PRDX4
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Medicine
Background:
- Osteoarthritis (OA) pathogenesis involves chondrocyte apoptosis driven by reactive oxygen species (ROS).
- Peroxiredoxin 4 (PRDX4) is crucial for mitigating intracellular ROS levels.
- Understanding PRDX4's role in interleukin 1β (IL-1β)-induced chondrocyte apoptosis is key for OA research.
Purpose of the Study:
- To investigate the protective effects of PRDX4 against IL-1β-induced apoptosis in chondrocytes.
- To elucidate the molecular mechanisms underlying PRDX4's function in chondrocyte survival.
Main Methods:
- Primary rat chondrocytes were cultured and manipulated to overexpress PRDX4.
- Cells were treated with IL-1β, and apoptosis, ROS production, nitric oxide (NO) levels, and protein expression were analyzed.
- Western blotting, flow cytometry, and colorimetric assays were employed.
Main Results:
- PRDX4 overexpression significantly reduced IL-1β-induced chondrocyte apoptosis.
- PRDX4 reversed IL-1β-mediated increases in ROS and NO production.
- PRDX4 modulated the expression of apoptosis-related proteins (Bcl-2, Bax) and activated the AKT signaling pathway.
Conclusions:
- PRDX4 exerts protective effects against IL-1β-induced chondrocyte apoptosis, partly via the phosphatidylinositol 3-kinase/AKT pathway.
- PRDX4 demonstrates potential as a therapeutic target for mitigating cartilage degeneration in osteoarthritis.
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