| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Research Abstract |
Bone homeostasis is maintained by both osteoclasts and osteoblasts. Osteoporosis is one of the bone diseases caused by collapse of bone homeostasis. Inhibitors of osteoclast differentiation are expected as new therapeutic agents for osteoporosis. We have found that TPh A inhibits osteoclast differentiation from bone marrow macrophages. We investigated the effects on RANKL-induced osteoclast differentiation of 50 TPh A derivatives in order to obtain a compound that inhibits osteoclastogenesis at a lower concentration than TPh A. We found that SUK-39 is the most potent osteoclastogenesis inhibitor. Moreover, RT-PCR analysis showed that SUK-39 suppressed RANKL-induced DC-STAMP and its transcription factor, c-fos mRNA level. These results indicated that SUK-39 inhibited osteoclast fusion by inhibiting expression of c-fos and subsequent DC-STAMP mRNA expression. SUK-39 would be a bioprobe for understanding the mechanisms of osteoclast fusion.
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