RND1 Induces Ferroptosis to Alleviate Inflammatory Response, Proliferation, Invasion, and Migration of Rheumatoid Synoviocytes.

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.