Transplantation of IL-1β siRNA-modified bone marrow mesenchymal stem cells ameliorates type II collagen-induced rheumatoid arthritis in rats

Shifeng Pan; Xuan Dong; Yan Wang; Tiansheng Zhou; Yuting Liu; An Zhou; Hua Xing

doi:10.3892/etm.2021.11062

Transplantation of IL-1β siRNA-modified bone marrow mesenchymal stem cells ameliorates type II collagen-induced rheumatoid arthritis in rats

Exp Ther Med. 2022 Feb;23(2):139. doi: 10.3892/etm.2021.11062. Epub 2021 Dec 14.

Authors

Shifeng Pan^{1

2}, Xuan Dong¹, Yan Wang¹, Tiansheng Zhou¹, Yuting Liu¹, An Zhou¹, Hua Xing^{1

2}

Affiliations

¹ Department of Basic Veterinary Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
² Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou, Jiangsu 225009, P.R. China.

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes erosion of articular cartilage and bone and has adverse effects on both patients and livestock animals. The aim of the present study was to investigate the role of interleukin-1β (IL-1β) in the pathogenesis of RA, and to further determine whether injection of IL-1β small interfering RNA (siRNA) or transplantation of IL-1β siRNA + bone marrow mesenchymal stem cells (BMSCs) can ameliorate RA in rats. A collagen-induced arthritis (CIA) rat model was established by injecting type II collagen for 4 weeks. Next, CIA rats were randomly divided into three groups and injected or transplanted with PBS, IL-1β siRNA and IL-1β siRNA + BMSCs for another 4 weeks. The CIA rat model was successfully established, as demonstrated by the higher toe swelling value, thymus and spleen/body weight, immobility time and serum IL-1β concentration, as well as lower body weight, climbing time and mRNA expression of programmed death-1 (PD-1), transforming growth factor-β1 (TGF-β1) and forkhead box protein 3 (Foxp3) in the spleen, compared with control rats. Furthermore, histopathology results demonstrated that joint swelling and redness were observed in the knee joints of CIA rats. H&E results revealed that CIA rats presented erosive destruction of the bone and ulceration of the articular cartilage. In addition, in vitro results demonstrated that IL-1β expression was successfully silenced after IL-1β siRNA transfection in lipopolysaccharide-stimulated BMSCs. When compared with the results of PBS rats, both IL-1β siRNA injection and IL-1β siRNA + BMSC transplantation significantly increased the body weight, climbing time and mRNA expression of PD-1, TGF-β1 and Foxp3 in the spleen, while significantly reduced the immobility time and serum IL-1β concentration. In addition, when compared with that of IL-1β siRNA injection, IL-1β siRNA + BMSC transplantation exhibited markedly higher therapeutic efficacy against CIA. These results demonstrated that higher IL-1β contributed to the pathogenesis of CIA, and that IL-1β siRNA injection ameliorated CIA, while its combination with BMSCs exerted synergistic effects, which may be beneficial against RA.

Keywords: bone marrow mesenchymal stem cells; collagen-induced arthritis; interleukin-1β small interfering RNA; rats; rheumatoid arthritis.

Grants and funding

Funding: The present work was supported by the National Natural Science Foundation of China (grant nos. 32072809, 31172284 and 31501923), the Natural Science Foundation of Jiangsu Province (grant nos. BK20211119 and BK20150443), China Postdoctoral Science Foundation Funded Project (grant no. 2015M581872) and Postdoctoral Science Foundation Funded Project of Jiangsu Province (grant no. 1501073A), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Yangzhou University Top-level Talents Support Program (2018) (grant no. 137080146) and Science and Technology Innovation Cultivation Fund of Yangzhou University (grant no. 2019CXJ140).