Peroxisome Functional Inhibition Alleviates TMJOA Cartilage Degradation.

This article investigates the role of peroxisomes in temporomandibular joint osteoarthritis (TMJOA), a degenerative cartilage disorder with limited treatment options. Using a mouse model and in vitro experiments, the study demonstrates that peroxisome dysfunction, induced by targeting the peroxisomal membrane protein PEX2, alleviates TMJOA progression by reducing cartilage degradation and inflammation. Mechanistically, peroxisome inhibition decreases palmitic acid (PA) levels, which otherwise activate the WNT/planar cell polarity (WNT/PCP) pathway via the JNK/c-JUN signaling axis, leading to upregulation of the downstream effector gene S100a4 that promotes extracellular matrix catabolism. The findings identify the peroxisome/PA/JNK/c-JUN/S100a4 axis as a critical mediator of TMJOA pathology and suggest peroxisomes as a promising therapeutic target for this condition.