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Updated: Feb 24, 2026

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
Targeting ORM1-CCR5 axis inhibits the aggressive phenotype of synovial fibroblasts and alleviates RA
Min Liu1, Yutong Chen2, Xuyang Ding2
1Department of Traditional Chinese Medicine, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang, China.
Objectives:
The present study focused on exploring the role of orosomucoid 1 (ORM1) in rheumatoid arthritis (RA).
Methods:
Differentially expressed genes in GSE15573 dataset were analyzed by bioinformatics. Fibroblast-like synoviocytes (FLS) from RA patients were stimulated with collagen-II, followed by quantification of ORM1 and C-C chemokine receptor 5 (CCR5) expressions. The interaction between ORM1 and CCR5 in FLS was examined by Co-immunoprecipitation. After ORM1 intervention or maraviroc treatment, the effect of ORM1 or CCR5 as well as their interplay in the stimulated cells was investigated using molecular experiments, methylthiazolyldiphenyl-tetrazolium bromide assay and transwell assay. Rats underwent collagen-induced arthritis (CIA) modeling. Arthritis index scoring, western blot assay and histopathological evaluation were performed in CIA rats with ORM1 or CCR5 knockdown.
Results:
ORM1 and CCR5 were highly expressed in collagen type II (CII)-stimulated FLS and synovial tissues of CIA rats. The expression of CCR5 was positively regulated by ORM1, and the interaction of ORM1 and CCR5 was confirmed. CII stimulation enhanced viability, migration and invasion of FLS, but these effects were antagonized in the absence of ORM1 or CCR5. Knockdown of ORM1 or CCR5 in CIA rats reduced arthritis index, while alleviating cartilage erosion, inflammatory infiltration and synovial hyperplasia of ankle joints.
Conclusions:
ORM1 deficiency suppresses the aggressive phenotype of FLS to reduce RA progression by downregulating CCR5.
Insights
Orosomucoid 1 (ORM1) deficiency suppresses rheumatoid arthritis (RA) progression by downregulating C-C chemokine receptor 5 (CCR5). This finding offers a new therapeutic target for RA treatment.
Area of Science:
- Immunology
- Molecular Biology
- Rheumatology
Background:
- Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and destruction.
- Fibroblast-like synoviocytes (FLS) play a crucial role in RA pathogenesis.
- The specific molecular mechanisms driving RA progression require further elucidation.
Purpose of the Study:
- To investigate the role of orosomucoid 1 (ORM1) in rheumatoid arthritis (RA).
- To explore the relationship between ORM1 and C-C chemokine receptor 5 (CCR5) in RA.
- To evaluate the therapeutic potential of targeting the ORM1-CCR5 axis in RA.
Main Methods:
- Bioinformatic analysis of gene expression datasets (GSE15573).
- In vitro studies using collagen-II stimulated RA FLS to assess ORM1 and CCR5 expression and interaction.
- In vivo studies using a collagen-induced arthritis (CIA) rat model with ORM1 or CCR5 knockdown.
Main Results:
- ORM1 and CCR5 were upregulated in stimulated FLS and CIA rat synovial tissues.
- ORM1 positively regulated CCR5 expression, and they interacted within FLS.
- ORM1 or CCR5 inhibition reduced FLS viability, migration, and invasion, and alleviated arthritis symptoms in CIA rats.
Conclusions:
- ORM1 promotes RA progression by enhancing FLS aggressive phenotype via CCR5.
- Targeting ORM1 or CCR5 demonstrates therapeutic potential for RA.
- ORM1 deficiency suppresses RA progression by downregulating CCR5.
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