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

ACPG activates PI3K and smad signaling pathway for progress of osteoblast differentiation

2008년 8월 7일 17시 43분 53초
33P171포 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
목 <발표Ⅰ>
저자 및
이수의, 심기석1, 김명희2, 백유미1, 김영섭3, 민용기1, 김성환1
충남대학교 생물학과, Korea
1한국화학연구원 화학유전체 연구실, Korea
2충남대학교 생화학과, Korea
3한국화학연구원 신약연구단, Korea
This study elucidates the roles of natural compounds such as ACPG in the differentiation of osteoblast. It would provide the initiative in the early drug discovery preventing the development of osteoporosis employing BMP-2 promoter screening system. The pharmacological use of natural compounds with anabolic activity could have a beneficial effect on bone health. Bone morphogenetic proteins (BMPs) are potent osteogenic agents advances the development of mesenchymal osteoprogenitor cells to osteoblast for bone formation. Runx2 expression is induced and complexed with SMAD by stimulation of BMP during this process. In this study, we identified ACPG accelerating osteoblast differentiation and investigated its activation mechanism in mouse osteoblastic MC3T3-E1 subclone 4 cells and mesenchymal progenitor cells C2C12. Induction of osteoblast differentiation was archived by either recombinant human BMP-2 (rhBMP-2) in C2C12 cells or ascorbic acid and β-glycerophosphate in MC3T3-E1 subclone 4 cells. Osteoblast differentiation and mineralization were determined by assaying alkaline phosphatase (ALP), Alizarin red S and von Kossa staining. Expression of osteoblast-related genes was evaluated by quantitative RT/PCR. Activation of phosphatidylinositol 3-kinase (PI3K), Akt, SMAD and mitogen-activated protein (MAP) kinases was assessed on Western blots for investigating intracellular signal transduction pathways. ACPG stimulated two distinct signaling pathways of osteoblast differentiation; one hand, ACPG activated PI3K-Akt and/or MAP kinase pathways eliciting the expression of BMP-2 gene in mouse osteoblastic MC3T3-E1 subclone 4 cells. The other hand, ACPG activated nuclear translocation of Smad and mRNA expression of Runx2 as well as BMP-2 in pluripotent mesenchymal precursor C2C12 cells. Furthermore, ACPG induced bone-forming activity in vivo in a mouse calvarial bone formation model. These results suggest that ACPG has the potential to enhance new bone formation by activating distinct signaling pathway on the progress of osteoblast differentiation