Peroxisome Functional Inhibition Alleviates TMJOA Cartilage Degradation

Area of Science:

• Biochemistry
• Molecular Biology
• Pathology

Background:

• Temporomandibular joint osteoarthritis (TMJOA) is a degenerative joint disease with poorly understood pathogenesis.
• Lipid metabolism disorders in chondrocytes, involving peroxisomes, are implicated in TMJOA development.
• Current TMJOA treatments are insufficient to restore joint structure.

Purpose of the Study:

• To investigate the role of peroxisomes in TMJOA pathogenesis.
• To elucidate the molecular mechanisms linking peroxisomes, lipid metabolism, and cartilage degradation in TMJOA.
• To identify potential therapeutic targets for TMJOA.

Main Methods:

• Established a TMJOA mouse model using unilateral anterior crossbite surgery.
• Utilized in vitro chondrocyte cultures and conditional knockout mice (Acan-CreER^T2 Pex2^f/f) to inhibit peroxisome function.
• Performed multiomics analysis, CUT&RUN qPCR, and dual-luciferase reporter assays to identify molecular pathways and interactions.

Main Results:

• Abnormal peroxisome quantity and function were observed in the TMJOA mouse model.
• Inhibition of peroxisome function alleviated OA-like damage and reduced palmitic acid (PA) levels.
• PA exposure induced OA-like phenotypes, activating the JNK/c-JUN signaling axis, leading to increased S100a4 expression and subsequent MMP13 upregulation, promoting TMJOA.

Conclusions:

• This study is the first to demonstrate the critical role of peroxisomes in TMJOA.
• The peroxisome/PA/JNK/c-JUN/S100a4 axis is identified as a key pathway in TMJOA cartilage degradation.
• This pathway represents a novel and promising therapeutic target for TMJOA.