Role of Anti‐Fractalkine Antibody in Suppression of Joint Destruction by Inhibiting Migration of Osteoclast Precursors to the Synovium in Experimental Arthritis

• Published in: Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2019-02, Vol.71 (2), p.222-231
• Main Authors: Hoshino‐Negishi, Kana, Ohkuro, Masayoshi, Nakatani, Tomoya, Kuboi, Yoshikazu, Nishimura, Miyuki, Ida, Yoko, Kakuta, Jungo, Hamaguchi, Akiko, Kumai, Minoru, Kamisako, Tsutomu, Sugiyama, Fumihiro, Ikeda, Wataru, Ishii, Naoto, Yasuda, Nobuyuki, Imai, Toshio
• Format: Article
• Language: English
• Subjects: Acid phosphatase; Acid phosphatase (tartrate-resistant); Acid resistance; Arthritis; Biocompatibility; Bone marrow; Cartilage; Cartilage oligomeric matrix protein; Collagen; Collagen (type II); CX3CR1 protein; Destruction; Endothelial cells; Fluorescein; Fractalkine; Immunization; Immunohistochemistry; Joint diseases; Joints (anatomy); Matrix metalloproteinase; Matrix protein; Metalloproteinase; Mice; Migration; Monoclonal antibodies; Osteoclasts; Osteoprogenitor cells; Plasma levels; Precursors; Proteins; Rheumatoid arthritis; Synovitis; Synovium
• ISSN: 2326-5191; 2326-5205
• DOI: 10.1002/art.40688

Objective To elucidate the role of the fractalkine (FKN)/CX3CR1 pathway in joint destruction in rheumatoid arthritis. Methods We examined the effect of treatment with anti–mouse FKN (anti‐mFKN) monoclonal antibody (mAb) on joint destruction and the migration of osteoclast precursors (OCPs) into the joint, using the collagen‐induced arthritis (CIA) model. DBA/1 mice were immunized with bovine type II collagen to induce arthritis, and then treated with anti‐mFKN mAb. Disease severity was monitored by arthritis score, and joint destruction was evaluated by soft x‐ray and histologic analyses. Plasma levels of joint destruction markers were assessed by enzyme‐linked immunosorbent assay. FKN expression on endothelial cells was detected by immunohistochemistry. Bone marrow–derived OCPs were labeled with fluorescein and transferred to mice with CIA, and the migration of the OCPs to the joints was then analyzed. Results Both prophylactic and therapeutic treatment with anti‐mFKN mAb significantly decreased the arthritis and soft x‐ray scores. Plasma levels of cartilage oligomeric matrix protein and matrix metalloproteinase 3 decreased after treatment with anti‐mFKN mAb. Histologic analysis revealed that anti‐mFKN mAb inhibited synovitis, pannus formation, and cartilage destruction, as well as suppressed bone damage, with a marked reduction in the number of tartrate‐resistant acid phosphatase–positive osteoclasts. Anti‐mFKN mAb strongly inhibited the migration of bone marrow–derived OCPs into the affected synovium. Conclusion Anti‐mFKN mAb notably ameliorates arthritis and joint destruction in the CIA model, as well as inhibits migration of OCPs into the synovium. These results suggest that inhibition of the FKN/CX3CR1 pathway could be a novel strategy for treatment of both synovitis and joint destruction in rheumatoid arthritis.