Silencing GJB2 attenuates IL-1β-induced chondrocyte injury by activating Nrf2/HO-1 signaling and preserving mitochondrial function.
Abstract
INTRODUCTION Mitochondrial oxidative stress is a key driver of inflammation-induced chondrocyte dysfunction and cartilage degeneration. However, the molecular regulators linking inflammatory signaling to mitochondrial impairment in chondrocytes remain incompletely understood. MATERIAL AND
Methods
Public transcriptomic datasets were analyzed using differential expression analysis, weighted gene co-expression network analysis (WGCNA), and screening for oxidative stress-related genes to identify osteoarthritis (OA)-associated hub genes. An IL-1β-induced CHON-001 chondrocyte injury model was established, and the GJB2 gene, which encodes connexin 26, was silenced using siRNA. Cell viability, oxidative stress, apoptosis, Nrf2/HO-1 signaling, and mitochondrial membrane potential were evaluated.
Results
Integrated bioinformatics analysis of multiple GEO datasets identified GJB2 as a key oxidative stress-related hub gene. IL-1β stimulation significantly increased GJB2 expression and induced oxidative stress, apoptosis, and mitochondrial dysfunction. GJB2 knockdown reduced reactive oxygen species (ROS) accumulation, attenuated inflammatory responses, inhibited apoptosis, restored Nrf2 nuclear translocation and HO-1 expression, and preserved mitochondrial membrane potential.
Conclusions
GJB2 promotes inflammation-associated oxidative injury and mitochondrial dysfunction in chondrocytes. Silencing GJB2 activates the Nrf2/HO-1 antioxidant pathway and confers cytoprotective effects, identifying GJB2 as a critical regulator and highlighting connexin-mediated redox signaling as a potential therapeutic target for cartilage degeneration.