| Budget Amount *help |
¥23,530,000 (Direct Cost: ¥18,100,000、Indirect Cost: ¥5,430,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2015: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2014: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
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| 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.
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