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  • 08월 28일 16시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

Dual effect of ARSA on the inhibition of osteoclastogenesis and bone resorption

2008년 8월 6일 12시 15분 30초
33P165포 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
목 <발표Ⅰ>
저자 및
김명희, 김영섭1, 민용기2, 김성환3
충남대학교 생화학과, Korea
1한국화학연구원 신약연구단, Korea
2한국화학연구원 생명화학연구단, Korea
3한국화학연구원 화학유전체 연구실, Korea
With the fact that the development of anti-resorptive agents from natural substances has gained more interest in the treatment of osteoporosis, here, 222 natural compounds were evaluated whether they have a potential to suppress RANKL-induced osteoclastogenesis in RAW264.7 cells. Of these compounds, ARSA significantly inhibited the RANKL-induced TRAP activity and formation of multinucleated osteoclast in a dose-dependent manner. In addition, it was shown to attenuate the RANKL-induced transcript levels of osteoclast specific genes, which have been known to be highly expressed in the process of osteoclastogenesis. Interestingly, ARSA was shown to inhibit the RANKL-induced activation of mitogen-activated protein kinase and NF-kappaB. The mRNA induction of AP-1 (especially, Fra-2) and NFATc1 by RANKL was also significantly prevented by ARSA. The inhibitory effect of ARSA on mouse bone marrow-derived osteoclastogenesis was also observed. Additionally, in mature osteoclasts, ARSA suppressed the bone resorption by inducing the osteoclast apoptosis with the activation of caspase 3 and 9. In conclusion, ARSA was shown to be with the dual activity; it inhibited the formation of osteoclast and the bone resorptive activity of mature osteoclasts and it suggested that ARSA could be useful to develop the therapeutic agents for osteoporosis.