Lacc1-Engineered Evs Reprogram Chondrocyte Metabolism In TMJOA

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative joint disorder involving cartilage degradation and inflammation. Metabolic dysregulation in chondrocytes contributes to TMJOA progression, yet the underlying mechanisms remain unclear. This study aimed to investigate metabolic imbalance in TMJOA cartilage and evaluate Lacc1-engineered extracellular vesicles (EVs) as a therapeutic strategy. RNA sequencing was performed to analyze metabolic changes in TMJOA cartilage. Macrophage-derived EVs overexpressing Lacc1 (OE-EVs) were constructed. In vitro, IL-1β-induced chondrocytes were treated with OE-EVs to assess inflammation, glycolysis, and mitochondrial function. In vivo therapeutic effects were evaluated in a TMJOA mouse model using micro-CT and histological analysis. Transcriptomic data revealed a shift toward glycolysis and suppressed oxidative phosphorylation in TMJOA cartilage. OE-EVs reduced IL-1β-induced inflammation, downregulated glycolytic enzymes, decreased mitochondrial superoxide levels, and restored mitochondrial structure. In vivo, OE-EVs alleviated cartilage damage and improved matrix integrity, with a 1.55-fold increase in toluidine blue-stained cartilage area compared to the TMJOA group. Lacc1-engineered EVs effectively reprogram mitochondrial metabolism and mitigate inflammation in TMJOA. This strategy holds promise for restoring chondrocyte metabolic homeostasis and promoting cartilage repair in degenerative joint disease.