Evaluation of the anti-RANKL monoclonal antibody in rheumatoid arthritis rats

Abstract

Objectives: In this study, we aimed to investigate the therapeutic effect of anti-receptor activator of nuclear factor kappa-κB ligand (RANKL) monoclonal antibodies R748-1-1-1, R748-1-1-2 and R748-1-1-3 on rheumatoid arthritis (RA) in a rat model.

Materials and methods: Gene cloning, hybridoma technology, affinity purification, enzyme-linked immunosorbent assay, general observation, hematoxylin-eosin staining, X-ray, and many other experimental techniques were used in this study.

Results: Improved collagen-induced arthritis (CIA) modeling was successfully constructed. The RANKL gene was cloned and the anti-RANKL monoclonal antibody was prepared. Following treatment with the anti-RANKL monoclonal antibody, the soft tissue swelling of the hind paws, the joint thickening, the narrowed joint gap, and the blurred edge of the bone joint were improved. The pathological changes such as synovial hyperplasia of fibrous tissue, cartilage and bone destruction were significantly decreased in the anti-RANKL monoclonal antibody-treated CIA group. Compared to the normal control group and phosphate buffer saline (PBS)-treated CIA group, the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1) in antibody-treated CIA group, positive drug-treated CIA group, and IgG-treated CIA group were decreased (p<0.05).

Conclusion: The anti-RANKL monoclonal antibody can promote the therapeutic effect of RA rats, indicating that the anti-RANKL monoclonal antibody has a certain potential value and may be beneficial to the further study of the mechanism of RA treatment.

Citation: Lv D, Zhao X. Evaluation of the anti-RANKL monoclonal antibody in rheumatoid arthritis rats. Arch Rheumatol 2023;38(1):22-31.

The approval of the study obtained the Ethics Committee of the Fourth Medical Center of PLA General Hospital (date: 20.07.2009, no: 0990). The study was conducted in accordance with the principles of the Declaration of Helsinki.

Data Sharing Statement:
The data that support the findings of this study are available from the corresponding author upon reasonable request.

Guarantor of integrity of the entire study, study concepts, study design, definition of intellectual content, clinical studies, experimental studies, data acquisition, data analysis, statistical analysis, manuscript preparation, manuscript editing: D.L.V.; Literature research: D.L.V., X.Z.

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

This study was supported by the National Natural Science Foundation of China (no. 61335011 & 31300691).