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GLX351322, a Novel NADPH Oxidase 4 Inhibitor, Attenuates TMJ Osteoarthritis by Inhibiting the ROS/MAPK/NF-κB
Jinze Zhen1, Xinwei Chen1, Yi Mao1
1Department of Oral Surgery, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
A novel NOX4 inhibitor, GLX351322 (GLX), reduces inflammation and oxidative stress in temporomandibular joint osteoarthritis (TMJOA) by targeting key signaling pathways. This suggests GLX is a promising therapeutic strategy for TMJOA.
Area of Science:
- Biomedical Research
- Molecular Biology
- Pathology
Background:
- Temporomandibular joint osteoarthritis (TMJOA) is a degenerative joint disease causing cartilage loss and inflammation.
- NADPH oxidase 4 (NOX4) is implicated in osteoarthritis pathogenesis via reactive oxygen species (ROS) production and inflammation.
- GLX351322 (GLX) is a novel NOX4 inhibitor with potential chondroprotective effects.
Purpose of the Study:
- To investigate the therapeutic potential of GLX on ROS production and inflammation in synovial macrophages.
- To evaluate the efficacy of GLX in an *in vitro* model of inflammation and an *in vivo* model of TMJ inflammation.
Main Methods:
- Assessed GLX's effect on lipopolysaccharide (LPS)-induced ROS production and inflammatory responses in synovial macrophages (*in vitro*).
- Evaluated GLX's impact on complete Freund's adjuvant (CFA)-induced TMJ inflammation in a mouse model (*in vivo*).
- Investigated the underlying signaling pathways, including ROS/MAPK/NF-κB.
Main Results:
- GLX effectively reduced LPS-induced ROS production and inflammation in synovial macrophages without cytotoxicity.
- GLX inhibited the ROS/MAPK/NF-κB signaling pathways.
- GLX treatment significantly attenuated TMJ synovial inflammation and protected condylar structures from damage *in vivo*.
Conclusions:
- GLX demonstrates therapeutic potential for TMJOA by inhibiting NOX4-mediated ROS production and inflammation.
- NOX4 inhibition represents a promising strategy for treating TMJOA and other inflammatory joint diseases.
