Qiuhua Chen,1,* Donglan Chen,2,* Sijie Wang,3 Xiaomei Huang,1 Liang Liang,1 Tong Xie,1 Jie Lu1 

1Department of Rheumatology and Immunology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524000, People’s Republic of China; 2Department of Infectious Diseases and Tropical Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524000, People’s Republic of China; 3Biomedical Diagnostic Center of Ultrastructure, Clinical Research and Experimental Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jie Lu, Department of Rheumatology and Immunology, Affiliated Hospital of Guangdong Medical University, 57 Renmin South Road, Xiashan District, Zhanjiang, Guangdong, 524000, People’s Republic of China, Email lujie2790@126.com

Background: Ferroptosis is involved in the occurrence and development of inflammatory arthritis. RND1 has been reported to possess pro-ferroptosis activity.
Objective: This study was designed to explore the role and the molecular mechanism of RND1 in rheumatoid arthritis (RA).
Methods: DBA/1 mice were exposed to type II collagen immunization. The pathological damage of the knee joints of mice was observed with H&E staining and RND1 expression in synovial tissues was detected using Western blot. In vitro, Western blot was used to measure RND1, ferroptosis-, migration- and inflammation-related proteins. The cell proliferation, migration and invasion were detected using CCK-8 method, EdU staining, wound healing and transwell assays. The levels of inflammatory factors were detected with ELISA and RT-qPCR. Relative iron level, GSH and MDA concentrations were detected with corresponding assay kits. BODIPY 581/591 C11 kit measured lipid ROS. 4-HNE and GPX4 expression were detected using immunofluorescence assay.
Results: This study found that RND1 expression was reduced in the synovial tissues of RA mice and human fibroblast-like MH7A synoviocytes. It was also found that the upregulation of RND1 inhibited the proliferation, migration, invasion and inflammatory response in rheumatoid synovial cells via ferroptosis.
Conclusion: Collectively, RND1 exerted protective impacts on RA, which might be mediated by ferroptosis.

Keywords: rheumatoid arthritis, RND1, ferroptosis, fibroblast-like synoviocytes