Complement factor H-related protein 5 alleviates joint inflammation and osteoclast differentiation by disrupting RANK-JNK signaling in collagen antibody-induced arthritis mouse model.

Autor: Jeon C; Hanyang University Institute for Rheumatology Research (HYIRR), Seoul, Republic of Korea; Deparment of Translational Medicine, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea., Kim D; Hanyang University Institute for Rheumatology Research (HYIRR), Seoul, Republic of Korea; Deparment of Translational Medicine, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea., Kim KM; Department of Rheumatology, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu, Republic of Korea; Eulji Rheumatology Research Institute, Eulji University, Uijeongbu, Republic of Korea., Lee SH; Hanyang University Institute for Rheumatology Research (HYIRR), Seoul, Republic of Korea., Lee JH; Department of Rheumatology, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu, Republic of Korea; Eulji Rheumatology Research Institute, Eulji University, Uijeongbu, Republic of Korea., Kim SH; Division of Rheumatology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea., Kim JS; School of Biological Sciences, Seoul National University, Seoul, Republic of Korea., Kang YM; Preclina Inc, Incheon, Republic of Korea; Division of Rheumatology, Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea., Jo S; Department of Biology, Soonchunhyang University, Asan, Republic of Korea. Electronic address: joejo0517@sch.ac.kr., Kim TH; Hanyang University Institute for Rheumatology Research (HYIRR), Seoul, Republic of Korea; Deparment of Translational Medicine, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea; Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea. Electronic address: thkim@hanyang.ac.kr., Son CN; Department of Rheumatology, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu, Republic of Korea; Eulji Rheumatology Research Institute, Eulji University, Uijeongbu, Republic of Korea. Electronic address: cnson@eulji.ac.kr.
Jazyk: angličtina
Zdroj: Cytokine [Cytokine] 2024 Dec; Vol. 184, pp. 156790. Date of Electronic Publication: 2024 Oct 25.
DOI: 10.1016/j.cyto.2024.156790
Abstrakt: Background: Complement Factor H-Related protein 5 (CFHR5) belongs to the factor H/CFHR family and regulates the complement system by modulating factor H's inhibitory activity against C3b. Despite its known role, the impact of CFHR5 on autoimmune arthritis and its relationship to pathophysiological changes in arthritis and bone loss remain unclear. This study aimed to assess the effect of CFHR5 on aggressive osteoclast activity and arthritis using a murine model of collagen antibody-induced arthritis (CAIA).
Methods: The effect of recombinant CFHR5 protein (rCFHR5) on arthritis were evaluated in CAIA. The mice were divided into three group and intraperitoneally treated with rCFHR5, methotrexate (MTX) as positive control or PBS as negative control. In the CAIA mouse model, the rCFHR5-treated group significantly reduced the incidence and clinical arthritis equivalent to the MTX group. Clinical arthritis scores, incidence and body weight were measured, and histological analysis of ankle joints was performed by Hematoxylin and Eosin (H&E) and Safranin O - Fast green (SOFG), Tartrate-resistant acid phosphatase (TRAP) staining and Immunohistochemistry. Moreover, to investigate the rCFHR5 role, we isolated murine osteoclast precursor cells (OCPs) from each group, induced osteoclasts with M-CSF and RANKL, and performed TRAP and F-actin staining. To verify the mechanism, mRNA and protein analyses were performed in OCPs.
Results: Histological examination of ankle joints revealed substantial reductions in synovial hyperplasia, bone marrow inflammation, bone erosion, cartilage destruction and TRAP-positive cells in the rCFHR5 group compared to the vehicle group. The ankle joints of the rCFHR5 group showed markedly decreased expression of proinflammatory cytokines (TNF-α, IL-1β and IL-6). Mechanically, treatment with rCFHR5 inhibited RANKL-mediated osteoclast differentiation from OCPs and disrupted the RANK-JNK signaling. These findings demonstrate that treatment with rCFHR5 attenuates joint inflammation and reduces osteoclast differentiation, indicating its potential anti-inflammatory effect in autoimmune arthritis models.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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