Anti-Fractalkine Antibody Suppresses Joint Destruction by Inhibiting Migration of Osteoclast Precursors to the Synovium in Experimental Arthritis.

OBJECTIVE: To elucidate the role of the fractalkine (FKN)-CX3CR1 pathway in joint destruction in rheumatoid arthritis, we examined the effect of treatment with anti-mouse FKN (mFKN) monoclonal antibody (mAb) on joint destruction and the migration of osteoclast precursors (OCPs) into the joint, using the collagen-induced arthritis (CIA) model.

METHODS: DBA/1 mice were immunized with bovine type II collagen to induce arthritis, then treated with anti-mFKN mAb. Disease severity was monitored by arthritis score, and joint destruction was evaluated by soft X-ray and histological analysis. Plasma levels of joint destruction markers were assessed by ELISA. FKN expression on endothelial cells was detected by immunohistochemistry. Furthermore, bone marrow-derived OCPs were labeled with fluorescein and transferred to CIA mice; then, their migration to the joints was analyzed.

RESULTS: Both prophylactic and therapeutic treatment with anti-mFKN mAb significantly reduced the arthritis and soft X-ray scores. Plasma levels of cartilage oligomeric matrix protein and matrix metalloproteinase-3 were decreased after treatment with anti-mFKN mAb. Histological analysis revealed that anti-mFKN mAb inhibited synovitis, pannus formation, and cartilage destruction, and that it suppressed bone damage, with marked reduction in the number of tartrate-resistant acid phosphatase+ osteoclasts. Anti-mFKN mAb strongly inhibited the migration of bone marrow-derived OCPs into the affected synovium.

CONCLUSION: Anti-mFKN mAb remarkably ameliorates arthritis and joint destruction in the CIA model, accompanied by reduced 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. This article is protected by copyright. All rights reserved.