The Nrf2 Pathway Alleviates Overloading Force-Induced TMJ Degeneration by Downregulating Oxidative Stress Reactions

Abstract

Minglu Xu,1,2,* Lingli Fang,1,2,* Qin Xue,1,2 Xuyang Zhang,1,2 Yao He1,3 1Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Oral Disease and Biomedical Sciences, Stomatological Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yao He, Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, 426 North of Songshi Avenue, Chongqing, 401147, People’s Republic of China, Email [email protected]: Oxidative stress is involved in the mechanisms associated with temporomandibular joint (TMJ) diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial oxidative stress marker, but the specific mechanisms of its regulation in the early stages of mandibular condylar cartilage (MCC) degeneration remain unclear. This study aimed to explore the regulatory role of Nrf2 and its related oxidative stress signaling pathway in the early stage of MCC degeneration.Materials and Methods: Overloading force-induced MCC degeneration was performed in wild-type and Nrf2 knockout mice, as well as in mice after treatment with the Nrf2 activator cardamonin. Changes in MCC degeneration and the expression of oxidative stress markers in the corresponding situations were observed.Results: Nrf2 and NADPH oxidase 2 (NOX2) expression were elevated during early MCC degeneration induced by an overloading force. MCC degeneration was aggravated when Nrf2 was knocked out, accompanied by increased NOX2 and superoxide dismutase 2 (SOD2) expression. The MCC degeneration process was alleviated after cardamonin treatment, with activation of the Nrf2 pathway and decreased NOX2 and SOD2 expression.Conclusion: Early MCC degeneration is accompanied by mild oxidative stress progression. Activated Nrf2 and related pathways could alleviate the degeneration of MCC.Keywords: NF-E2-related factor 2, oxidative stress, temporomandibular joint, cartilage, mechanical force

Keywords

• nf-e2-related factor 2
• oxidative stress
• temporomandibular joint
• cartilage
• mechanical force