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“ 백승화 논문 PLoS One published now ”
Baek SH, Choi SW, Park SJ, Lee SH, Kim SH.

Quinoline compound KM11073 enhances BMP-2-dependent osteogenic differentiation of C2C12 cells via activation of p38 signaling and exhibits in vivo bone forming activity.

PLoS One,10(3), e0120150.
ISSN=1932-6203  
IF=3.73
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PLoS One. 2015 Mar 19;10(3):e0120150. doi: 10.1371/journal.pone.0120150. eCollection 2015.

Quinoline Compound KM11073 Enhances BMP-2-Dependent Osteogenic Differentiation of C2C12 Cells via Activation of p38 Signaling and Exhibits In Vivo Bone Forming Activity.

Baek SH1, Choi SW2, Park SJ3, Lee SH4, Chun HS5, Kim SH2.

Author information
1Laboratory of Translational Therapeutics, Pharmacology Research Center, Korea Research Institute of Chemical Technology, Daejeon, 305-600, Republic of Korea; Department of Food Science & Biotechnology, Kyungpook National University, Daegu, 702-701, Republic of Korea.
2Laboratory of Translational Therapeutics, Pharmacology Research Center, Korea Research Institute of Chemical Technology, Daejeon, 305-600, Republic of Korea.
3Department of Histology, College of Veterinary Medicine, Kyungpook National University, Daegu, 702-701, Republic of Korea.
4Department of Food Science & Biotechnology, Kyungpook National University, Daegu, 702-701, Republic of Korea.
5Alternative Toxicological Methods Research Center, Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, 305-600, Republic of Korea.

Abstract

Recombinant human bone morphogenetic protein (rhBMP)-2 has been approved by the FDA for clinical application, but its use is limited due to high cost and a supra-physiological dose for therapeutic efficacy. Therefore, recent studies have focused on the generation of new therapeutic small molecules to induce bone formation or potentiate the osteogenic activity of BMP-2. Here, we show that [4-(7-chloroquinolin-4-yl) piperazino][1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl]methanone (KM11073) strongly enhances the BMP-2-stimulated induction of alkaline phosphatase (ALP), an early phase biomarker of osteoblast differentiation, in bi-potential mesenchymal progenitor C2C12 cells. The KM11073-mediated ALP induction was inhibited by the BMP antagonist noggin, suggesting that its osteogenic activity occurs via BMP signaling. In addition, a pharmacological inhibition study suggested the involvement of p38 activation in the osteogenic action of KM11073 accompanied by enhanced expression of BMP-2, -6, and -7 mRNA. Furthermore, the in vivo osteogenic activity of KM11073 was confirmed in zebrafish and mouse calvarial bone formation models, suggesting the possibility of its single use for bone formation. In conclusion, the combination of rhBMP-2 with osteogenic small molecules could reduce the use of expensive rhBMP-2, mitigating the undesirable side effects of its supra-physiological dose for therapeutic efficacy. Moreover, due to their inherent physical properties, small molecules could represent the next generation of regenerative medicine.
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