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Mol. Cells 2013; 36(5): 417-423
Published online October 22, 2013
https://doi.org/10.1007/s10059-013-0184-9
© The Korean Society for Molecular and Cellular Biology
The Protein Kinase 2 Inhibitor CX-4945 Regulates Osteoclast and Osteoblast Differentiation In Vitro
Drug repositioning can identify new therapeutic applica-tions for existing drugs, thus mitigating high R&D costs. The Protein kinase 2 (CK2) inhibitor CX-4945 regulates human cancer cell survival and angiogenesis. Here we found that CX-4945 significantly inhibited the RANKL-indu-ced osteoclast differentiation, but enhanced the BMP2-induced osteoblast differentiation in a cell culture model. CX-4945 inhibited the RANKL-induced activation of TRAP and NFATc1 expression accompanied with sup-pression of Akt phosphorylation, but, in contrast, it enhanced the BMP2-mediated ALP induction and MAPK ERK1/2 phosphorylation. CX-4945 is thus a novel drug candidate for bone-related disorders such as osteoporosis.
Keywords CK2, CX-4945, differentiation, osteoblast, osteoclast
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Research Article
Mol. Cells 2013; 36(5): 417-423
Published online November 30, 2013 https://doi.org/10.1007/s10059-013-0184-9
Copyright © The Korean Society for Molecular and Cellular Biology.
The Protein Kinase 2 Inhibitor CX-4945 Regulates Osteoclast and Osteoblast Differentiation In Vitro
You Hwa Son, Seong Hee Moon, and Jiyeon Kim
1Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Daejeon 301-746, Korea, 2Laboratory of Translational Therapeutics, Pharmacological Research Center, Bio-Organic Science Division, Korea Research Institute of Chemical Technology, Daejeon 305-600, Korea, 3These authors contributed equally to this work.
Abstract
Drug repositioning can identify new therapeutic applica-tions for existing drugs, thus mitigating high R&D costs. The Protein kinase 2 (CK2) inhibitor CX-4945 regulates human cancer cell survival and angiogenesis. Here we found that CX-4945 significantly inhibited the RANKL-indu-ced osteoclast differentiation, but enhanced the BMP2-induced osteoblast differentiation in a cell culture model. CX-4945 inhibited the RANKL-induced activation of TRAP and NFATc1 expression accompanied with sup-pression of Akt phosphorylation, but, in contrast, it enhanced the BMP2-mediated ALP induction and MAPK ERK1/2 phosphorylation. CX-4945 is thus a novel drug candidate for bone-related disorders such as osteoporosis.
Keywords: CK2, CX-4945, differentiation, osteoblast, osteoclast
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