Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/29671
English  |  正體中文  |  简体中文  |  Items with full text/Total items : 18034/20233 (89%)
Visitors : 23341724      Online Users : 441
RC Version 7.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
  • Adv. Search
    HomeLoginUploadHelpAboutAdminister Goto mobile version
    Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/29671


    Title: KMUP-1 Promotes Osteoblast Differentiation Through cAMP and cGMP Pathways and Signaling of BMP-2/Smad1/5/8 and Wnt/-Catenin
    Authors: Liou, Shu-Fen
    Hsu, Jong-Hau
    Chu, Hsin-Chieh
    Lin, Hung-Hong
    Chen, Ing-Jun
    Yeh, Jwu-Lai
    Contributors: 藥學系
    Keywords: Protein-Kinase-G
    Transcription Factor
    K+ Channels
    Cyclic-Gmp
    Osteoprogenitor Cells
    Rat Osteoblast
    Smooth-Muscle
    Bone Mass
    Involvement
    Expression
    Date: 2015-09
    Issue Date: 2016-04-19 19:04:03 (UTC+8)
    Publisher: Wiley-Blackwell
    Abstract: Phosphodiesterase (PDE) inhibitors have been suggested as a possible candidate for the treatment of osteopenia, including osteoporosis. KMUP-1 is a novel xanthine derivative with inhibitory activities on the PDE 3, 4, and 5 iso-enzymes to suppress the degradation of cAMP and cGMP. This study aimed to investigate the effect of KMUP-1 on osteoblast differentiation and the underlying cellular and molecular mechanisms. Primary osteoblasts and osteoblastic MC3T3-E1 cells were examined. KMUP-1 enhanced alkaline phosphatase (ALP) activity and mineralization compared to untreated controls in primary osteoblasts and MC3T3-E1 cells. KMUP-1 also increased the mRNA expression of the osteoblastic differentiation markers, including collagen type 1a, ALP, osteocalcin, osteoprotegerin, BMP-2, and Runx2, a key transcription regulator for osteoblastic differentiation. The osteogenic effect of KMUP-1 was abolished by BMP signaling inhibitor, noggin. Furthermore, we found that KMUP-1 upregulated Smad1/5/8 phosphorylations with subsequent BRE-Luc activation confirmed by transient transfection assay. In addition, KMUP-1 inactivated glycogen synthase kinase-3 (GSK-3), with associated nuclear translocation of -catenin. Co-treatment with H89 and KT5823, cAMP and cGMP pathway inhibitors, respectively, reversed the KMUP-1-induced activations of Smad1/5/8, -catenin, and Runx2. The findings demonstrate for the first time that KMUP-1 can promote osteoblast maturation and differentiation in vitro via BMP-2/Smad1/5/8 and Wnt/-catenin pathways. These effects are mediated, in part, by the cAMP and cGMP signaling. Thus, KMUP-1 may be a novel osteoblast activator and a potential new therapy for osteoporosis
    Relation: Journal of Cellular Physiology, v.230 n.9, pp.2038-2048
    Appears in Collections:[Dept. of Pharmacy] Periodical Articles

    Files in This Item:

    File Description SizeFormat
    index.html0KbHTML1302View/Open


    All items in CNU IR are protected by copyright, with all rights reserved.


    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback