Targeting Txnip-mediated metabolic reprogramming has therapeutic potential for osteoarthritis.

Abstract

Osteoarthritis (OA) inflammatory microenvironment triggered glucose metabolism and mitochondrial dysfunction in chondrocytes, leading to a shift of metabolic tendency between oxidative phosphorylation and anaerobic glycolysis. Thioredoxin-interacting protein (Txnip) increased production of reactive oxygen species (ROS), which exacerbates oxidative stress, inflammation and further accelerates cartilage degeneration and extracellular matrix (ECM) degradation. Txnip expression is also positively correlated with several critical pathological glucose and lipid metabolism processes beyond inflammation and endoplasmic reticulum stress (ERS). While the role of Txnip-mediated chondrocyte metabolic reprogramming in OA has not been explored. This study focuses on the unexplored role of Txnip-mediated chondrocyte metabolic reprogramming in chondrogenesis and ECM deposition. The study reveals that upregulated glycolysis after Txnip knockdown significantly contributes to mouse chondrogenesis and ECM deposition. Moreover, verapamil, a clinically used drug that targets Txnip, shows potential for treating mouse OA. These findings suggest that targeting Txnip-mediated metabolic reprogramming could offer a novel therapeutic strategy for OA treatment.