Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.

Ablation of CCR2 Exaggerates Arthritis and Enhances Bone Destruction in IL-1ra/ Mice

Hiroshi1,  Fujii, Tomohisa2,  Baba, Ryoko1,  Hamano, Kazunori1,  Yamada, Tamehito1,  Onoe, Kawano1,  Mitsuhiro, Masakazu3,  Yamagishi

Kanazawa University Graduate School of Medicine, Kanazawa, Japan
Cancer Research Institute, Kanazawa University, Kanazawa, Japan
Kanazawa University Graduate School of Medicine, Japan


Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the infiltration of macrophages and neutrophils into the joint space. Chemokine receptors, CCR2 and CX3CR1, are expressed on macrophages infiltrating into the synovium of RA patients. However, it still remains unclear on the roles of CCR2- or CX3CR1-mediated signals in RA. Hence, we investigated the roles of CCR2- or CX3CR1-mediated signals in arthritis developed spontaneously in IL-1ra-deficient mice, by ablating CCR2 or CX3CR1 gene in IL-1ra-deficient mice.


IL1ra-deficient, IL1ra-CX3CR1-double deficient and IL1ra-CCR2-double deficient mice underwent clinical assessment of arthritis, histological examination, assessment of bone mineral density, determination of cytokine and protein levels and assessment of osteoclastogenesis.


Consistent with the previous report, IL-1ra-deficient mice developed multiple arthritis until 12 weeks after birth. Ablation of CCR2 gene but not CX3CR1 gene exaggerated arthritis in IL-1ra-deficient mice, as evidenced by augmented arthritis clinical scores and histopathological scores characterized by an aberrant neutrophil accumulation. Moreover, IL-1ra-CCR2-double deficient mice exhibited lower bone mineral density on computer tomography and higher serum concentration of cartilage oligomeric matrix protein, than IL-1ra-deficient mice. Furthermore, tartrate-resistant acid phosphatase-positive osteoclasts were increased in the joints of IL-1ra-CCR2-double deficient mice, compared with IL-1ra-deficient mice. Immunohistochemical analysis revealed that neutrophils in the inflamed joint expressed RANKL and ADAM 8, factors crucially involved in osteoclast formation.


Ablation of CCR2 could aggravate arthritis developed spontaneously in IL-1ra-deicient mice, with enhanced accumulation of neutrophils, which express RANKL and ADAM 8, thereby inducing bone destruction.

To cite this abstract, please use the following information:
Hiroshi, Fujii, Tomohisa, Baba, Ryoko, Hamano, Kazunori, Yamada, Tamehito, Onoe, Kawano, Mitsuhiro, et al; Ablation of CCR2 Exaggerates Arthritis and Enhances Bone Destruction in IL-1ra/ Mice [abstract]. Arthritis Rheum 2009;60 Suppl 10 :42
DOI: 10.1002/art.25125

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