Background: Complement factor H-related protein 5(CFHR5), a member of complement factor H, plays an important role in regulating the innate immune system. CFHR5 is known to have an anti-inflammatory effect by binding to complement C3, an inflammatory response protein and activator for osteoclasts. However, the impact of CFHR5 on the autoimmune based on arthritis and its relation to the pathophysiological changes in arthritis and bone loss features remain largely unknown.

Objectives: The aim of this study was to evaluate the effect of CFHR5 on the aggressive osteoclast and arthritis in the murine Collagen antibody-induced arthritis (CAIA).

Methods: The effect of recombinant CFHR5 protein (rCHFR5) on arthritis were evaluated in CAIA. The mice were divided into three group and intraperitoneally treated with low dose 0.5 mg/kg, high 1.5 mg/kg, or methotrexate as positive control. Clinical arthritis scores and body weight were measured, and histological changes of ankle joints were performed by Hematoxylin and Eosin (H&E) Toluidine Blue, and Tartrate-resistant acid phosphatase (TRAP) stain. Moreover, to investigate the CFHR5 role, we isolated murine bone marrow-derived macrophages (BMM), induced osteoclasts with rCHFR5 in the presence of Macrophage Colony-Stimulating Factor (M-CSF) and Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL) treatments, and subjected to mRNA and protein analysis of RANKL-related singling.

Results: The therapeutic efficacy of rCFHR5 (0.5 mg/kg) and rCFHR5 (1.5 mg/kg) was compared with that of the vehicle control, which revealed reduction in CAI score of both models. The incidence of arthritis in CAIA was reduced in the rCFHR5 (0.5 mg/kg) low-dose group compared to the vehicle. The rCFHR5-treated CAIA group did not show any significant change in body weight, but histological analysis in hind paw revealed a significant reduction in parameters including synovial hyperplasia, pannus formation, bone erosion, and cartilage destruction in rCFHR5-treated CAIA group compared to control vehicle group. In addition, the expression of proinflammatory cytokine (TNF-α, IL-1α, and IL-6) was dramatically reduced in joint ankle of rCFHR5-treated CAIA group. Mechanically, rCFHR5 decreased osteoclast differentiation of BMM by disrupting RANKL-JNK signaling activation.

Conclusion: In this study, we demonstrated that rCFHR5 administration attenuated joint inflammation and reduced osteoclasts differentiation in both In vivo and In vitro mouse model, indicating that CFHR5 has an anti-inflammatory effect on arthritis of peripheral joints.

REFERENCES: NIL.

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Acknowledgements: NIL.

Disclosure of Interests: None declared.