Analysis on the influence of RANKL reverse signaling in the development of rheumatoid arthritis

2017 Fiscal Year Final Research Report

• Project/Area Number: 26713045
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: Ikebuchi Yuki 東京大学, 医学部附属病院, 助教 (20645725)
• Research Collaborator: HONMA Masashi 東京大学, 医学部附属病院, 講師 (60401072)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: RANKL / 関節リウマチ / 細胞分化制御

Outline of Final Research Achievements

We revealed that RANKL reverse signaling plays the significant roles in the cycle of bone resorption and formation. RANKL is expressed in chondrocytes, activated T cells, and synovial fibroblasts as well as osteoblasts/osteocytes. In the development of rheumatoid arthritis, the imbalance of these cells differentiation and activities is observed, therefore, we analyzed on the pathological influence of RANKL reverse signaling in each cell line. At first, multimeric anti-RANKL antibody were designed for cross-linking RANKL molecules. In fact, scDb-Fc protein, which was composed of four scFv domains connected with Fc, showed strong potential of RANKL reverse signaling. Using this agonistic moiety, we confirmed the effect of RANKL reverse signaling in each cell line. Furthermore, collagen-induced arthritis model mice were used for evaluating the effects of RANKL reverse signaling in vivo.

Free Research Field

骨・軟骨代謝