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. 2025 Feb 21:18:2647-2659.
doi: 10.2147/JIR.S500630. eCollection 2025.

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

Qiuhua Chen #  1 , Donglan Chen #  2 , Sijie Wang  3 , Xiaomei Huang  1 , Liang Liang  1 , Tong Xie  1 , Jie Lu  1
Affiliations

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

Qiuhua Chen et al. J Inflamm Res. .

Abstract

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: RND1; ferroptosis; fibroblast-like synoviocytes; rheumatoid arthritis.

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Conflict of interest statement

The authors declare no competing interests in this work.

Figures

None
Graphical abstract
Figure 1
Figure 1
RND1 expression is downregulated in the joint tissues of RA mice. (A) The symptoms of CIA mice were observed. (B) The pathological features of the keen joints of CIA mice were detected using H&E staining. The black arrows point to the pannus. (C) The protein expression of RND1 in synovial tissues of CIA mice was detected using Western blot. (D) The expressions of ferroptosis-related proteins were detected using Western blot. (E) Immunohistochemical analysis for GPX4. **P<0.01 and ***P<0.001.
Figure 2
Figure 2
RND1 expression is downregulated in RA-FLSs. (A) The mRNA and protein expressions of RND1 in RA-FLSs were detected using RT-qPCR and Western blot. (B) The expressions of ferroptosis-related proteins were detected using Western blot. **P<0.01 and ***P<0.001.
Figure 3
Figure 3
RND1 overexpression inhibits the proliferation, migration and invasion in RA-FLSs. (A) The transfection efficacy of Ov-RND1 was detected using RT-qPCR and Western blot. (B) The cell viability was detected using CCK-8 assay. (C) The cell proliferation was detected using EdU staining. (D) The cell migration and invasion were detected using wound healing and transwell. (E) The expressions of MMP2 and MMP9 were detected using Western blot. *P<0.05 and ***P<0.001.
Figure 4
Figure 4
RND1 overexpression inhibits the inflammatory release in RA-FLSs. (A) The levels of inflammatory factors were detected using ELISA. (B) The mRNA expressions of inflammatory factors were detected using RT-qPCR. (C) The expressions of inflammation-related proteins were detected using Western blot. ***P<0.001.
Figure 5
Figure 5
RND1 overexpression promotes ferroptosis in RA-FLSs. (A) The iron level and MDA and GSH concentrations were detected using corresponding assay kits. (B) The lipid ROS was detected using BODIPY 581/591 C11 kit. (C) 4-HNE expression was detected using immunofluorescence assay. (D) The expressions of ferroptosis-related proteins were detected using Western blot. (E) The GPX4 expression was detected using immunofluorescence assay. ***P<0.001.
Figure 6
Figure 6
RND1 overexpression inhibits the proliferation, migration and invasion in RA-FLSs via ferroptosis. (A) The cell viability was detected using CCK-8 assay. (B and C) The cell proliferation was detected using EdU staining. (D and E) The cell migration and invasion were detected using wound healing and transwell. (F and G) The expressions of MMP2 and MMP9 were detected using Western blot. **P<0.01 and ***P<0.001, #P<0.01 ##P<0.01 and ###P<0.001.
Figure 7
Figure 7
RND1 overexpression inhibits the inflammatory release in RA-FLSs via ferroptosis. (A and B) The levels of inflammatory factors were detected using ELISA. (C and D) The mRNA expressions of inflammatory factors were detected using RT-qPCR. (E and F) The expressions of inflammation-related proteins were detected using Western blot. *P<0.05, **P<0.01 and ***P<0.001.
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