Acceleration of osteoblast differentiation by a novel osteogeniccompound, DMP-PYT, through activation of both the BMP and Wnt pathways

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/474183.do
DOI
10.1038/s41598-017-08190-9
Title
Acceleration of osteoblast differentiation by a novel osteogeniccompound, DMP-PYT, through activation of both the BMP and Wnt pathways
Description
We thank Drs Hyun-Mo Ryoo and Dae-Sik Lim for providing 6 x OSE2-luc andantibodies against pSMAD2/3 and SMAD2/3, and also thank Drs Myung Ae Bae(KRICT) and Cheol-Hee Kim (Chungnam National University) for sharing thezebrafish facility and for conducting adult zebrafish experiment andproviding zebrafish fertilized eggs. We appreciate the chemical libraryof Korea Chemical Bank in KRICT. This work was supported by Mid-careerresearch program of the National Research Foundation (ESH,NRF-2013R1A2A2A01068302) and National Research Council of Science &Technology (CRC-15-02-KRIBB) grant funded by the Korea government.
abstract
Osteoblast differentiation is regulated through the successive activation of signaling molecules by a complex interplay of extracellular signals such as bone morphogenetic protein (BMP) and Wnt ligands. Numerous studies have identified natural as well as synthetic compounds with osteogenic activity through the regulation of either BMP/SMADs or the Wnt/beta-catenin pathway. Here, we attempted to isolate small molecules that concurrently activated both SMADs and beta-catenin, which led to the discovery of a novel potent osteogenic compound, DMP-PYT. Upon BMP2 stimulation, DMP-PYT substantially increased osteoblast differentiation featured by enhanced expression of osteoblast-specific genes and accelerated calcification through activation of BMPs expression. DMP-PYT promoted BMP2-induced SMAD1/5/8 phosphorylation and beta-catenin expression, the latter in a BMP2-independent manner. DMP-PYT alone enhanced nuclear localization of beta-catenin to promote the DNA-binding and transcriptional activity of T-cell factor, thereby resulting in increased osteoblast differentiation in the absence of BMP2. Most importantly, DMP-PYT advanced skeletal development and bone calcification in zebrafish larvae. Conclusively, DMP-PYT strongly stimulated osteoblast differentiation and bone formation in vitro and in vivo by potentiating BMP2-induced activation of SMADs and beta-catenin. These results suggest that DMP-PYT may have beneficial effects for preventing and for treating osteoporosis.
provenance
Made available in Cube on 2018-09-28T10:39:22Z (GMT). No. of bitstreams: 0
language
English
author
Bae, Su Jung
Kim, Hye Joo
Won, Hee Yeon
Min, Yong Ki
Hwang, Eun Sook
accessioned
2018-09-28T10:39:22Z
available
2018-09-28T10:39:22Z
issued
2017
citation
SCIENTIFIC REPORTS(7)
issn
2045-2322
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/474183.do
Funder
교육부
Funding Program
BK21플러스사업(0.5)
Project ID
1345274048
Jurisdiction
Rep.of Korea
Project Name
Ewha Graduate Program of Prospective Pharmaceutical Sciences
rights
openAccess
type
article


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