Complement factor H-related protein 5 alleviates joint inflammation and osteoclast differentiation by disrupting
Chanhyeok Jeon1, Dongju Kim1, Kyung-Me Kim2
1Hanyang 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.
Insights
Complement Factor H-Related protein 5 (CFHR5) significantly reduced joint inflammation and bone erosion in a mouse model of autoimmune arthritis. This protein also inhibited osteoclast differentiation, suggesting a potential therapeutic role in treating arthritis.
Area of Science:
- Immunology
- Rheumatology
- Osteology
Background:
- Complement Factor H-Related protein 5 (CFHR5) is part of the factor H/CFHR family, regulating the complement system.
- The specific role of CFHR5 in autoimmune arthritis and its effect on bone loss were previously unclear.
Purpose of the Study:
- To investigate the therapeutic potential of CFHR5 in autoimmune arthritis.
- To assess CFHR5's impact on osteoclast activity and related pathological changes in a murine model.
Main Methods:
- A collagen antibody-induced arthritis (CAIA) mouse model was used.
- Mice were treated with recombinant CFHR5 (rCFHR5), methotrexate (positive control), or PBS (negative control).
- Arthritis severity, joint histology, osteoclast differentiation, and signaling pathways were analyzed.
Main Results:
- rCFHR5 treatment significantly reduced arthritis incidence, clinical scores, and joint damage, comparable to methotrexate.
- Histological analysis showed decreased inflammation, bone erosion, and osteoclast markers in rCFHR5-treated mice.
- rCFHR5 inhibited RANKL-mediated osteoclast differentiation and disrupted RANK-JNK signaling.
Conclusions:
- CFHR5 demonstrates significant anti-inflammatory and bone-protective effects in autoimmune arthritis.
- CFHR5 attenuates joint inflammation by reducing osteoclast differentiation and activity.
- CFHR5 shows promise as a novel therapeutic agent for autoimmune arthritis.
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.
