Effects of antibody to receptor activator of nuclear factor κ-B ligand on inflammation and cartilage degradation in collagen antibody-induced arthritis in mice

Abstract

Background: Rheumatoid arthritis (RA) is an inflammatory disease that leads to destruction of both articula cartilage and bone tissues. In rheumatic joints, synoviocytes and T-lymphocytes as well as bone cells produce th receptor activator of nuclear factor ?-B (RANK) ligand (RANKL), which binds to RANK on the surface of osteoclast and their precursor cells to induce differentiation and activation of osteoclasts. Hence, inhibition of RANKL may be promising approach to suppress osteolysis in RA. On the other hand, RANKL production by lymphocytes indicate the possibility that its inhibition would be effective to suppress inflammation in RA. In addition, it has been reporte that cathepsin K, a predominant cysteine protease in osteoclasts, is involved in cartilage destruction in RA mode mice. Here, we evaluated the effects of an anti-RANKL antibody on inflammation in footpads and degradation o articular cartilage in RA model mice Results: We induced arthritis in mice by injection of anti-Type II collagen antibodies and lipopolysaccharide (LPS) Inhibition of RANKL by an anti-RANKL antibody (OYC1, Oriental Yeast, Tokyo, Japan) was confirmed by increase bone volume in the metaphysis of tibias. Swelling in either limb until day 14 was seen in 5 of 6 mice injected wit anti-collagen antibodies and LPS without treatment with OYC1, while that was seen in 4 of 5 mice treated wit OYC1. The average arthritis scores on day 14 in those groups were 2.17 and 3.00, respectively, indicating that OYC did not ameliorate inflammation in the limbs. Histological analyses indicated that OYC1 does not protect articula cartilage from destruction in mice with arthritis Conclusions: Our present study failed to show the effectiveness of an anti-RANKL antibody to ameliorate inflammatio in the limbs or protect articular cartilage from degradation in a collagen antibody-induced arthritis mouse model.