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Potent osteogenic activity of a novel imidazobenzimidazole derivative, IBIP

Title
Potent osteogenic activity of a novel imidazobenzimidazole derivative, IBIP
Authors
Bae S.J.Min Y.K.Hwang E.S.
Ewha Authors
황은숙
SCOPUS Author ID
황은숙scopus
Issue Date
2017
Journal Title
Biochemical and Biophysical Research Communications
ISSN
0006-291XJCR Link
Citation
vol. 487, no. 2, pp. 409 - 414
Keywords
BMP2ERKIBIPOsteoblast differentiationSMAD
Publisher
Elsevier B.V.
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Bone mass is controlled by a balance between bone resorption and formation by osteoclasts and osteoblasts, respectively. An imbalance between osteoblasts and osteoclasts increases the risk of osteoporosis and fractures. Although inhibition of osteoclasts is beneficial for preventing and treating osteoporosis, enhanced bone formation through activation of osteoblast differentiation can be a more promising therapeutic approach. In this study, we attempted to isolate small molecules that promote osteoblast differentiation and found that IBIP (3-(2,3-dimethoxyphenyl)-1-[9-methyl-2-phenyl-9H-imidazo[1,2-a]benzimidazol-3-yl]-2-propen-1-one) was a potent activator of osteoblast differentiation. Upon bone morphogenetic protein-2 (BMP2) stimulation, IBIP promoted osteoblast differentiation and increased the expression of osteoblast-specific gene markers, such as osterix and alkaline phosphatase, in a dose-dependent manner. The phosphorylation of SMADs and extracellular signal-regulated kinase (ERK) increased after IBIP treatment. While enhanced SMAD phosphorylation by IBIP was abolished by a BMP inhibitor, IBIP-induced ERK phosphorylation was sustained in the presence of this inhibitor, but was decreased by an ERK kinase inhibitor. Suppression of IBIP-induced SMAD and ERK phosphorylation diminished osteoblast differentiation. Most importantly, IBIP enhanced bone formation and calcification in a BMP2-independent manner in vitro and advanced the skeletal development of zebrafish larvae in vivo. Collectively, IBIP may have beneficial effects on bone loss through potentiation of bone formation. © 2017 Elsevier Inc.
DOI
10.1016/j.bbrc.2017.04.075
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약학대학 > 약학과 > Journal papers
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