U0126 promotes osteogenesis of rat bone-marrow-derived mesenchymal stem cells by activating BMP/Smad signaling pathway
详细信息    查看全文
  • 作者:Liangliang Xu ; Yang Liu ; Yonghui Hou ; Kuixing Wang ; Yinmei Wong…
  • 关键词:U0126 ; ERK1/2 ; Osteogenesis ; Mesenchymal stem cells ; BMP/Smad ; Rat (Sprague ; Dawley)
  • 刊名:Cell and Tissue Research
  • 出版年:2015
  • 出版时间:February 2015
  • 年:2015
  • 卷:359
  • 期:2
  • 页码:537-545
  • 全文大小:2,190 KB
  • 参考文献:1. Augello A, De Bari C (2010) The regulation of differentiation in mesenchymal stem cells. Hum Gene Ther 21:1226-238 CrossRef
    2. Benisch P, Schilling T, Klein-Hitpass L, Frey SP, Seefried L, Raaijmakers N, Krug M, Regensburger M, Zeck S, Schinke T, Amling M, Ebert R, Jakob F (2012) The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors. PLoS One 7:e45142 CrossRef
    3. Chen D, Zhao M, Mundy GR (2004) Bone morphogenetic proteins. Growth Factors 22:233-41 CrossRef
    4. Dalle Carbonare L, Valenti MT, Zanatta M, Donatelli L, Lo Cascio V (2009) Circulating mesenchymal stem cells with abnormal osteogenic differentiation in patients with osteoporosis. Arthritis Rheum 60:3356-365 CrossRef
    5. Dang ZC, Lowik CW (2004) Differential effects of PD98059 and U0126 on osteogenesis and adipogenesis. J Cell Biochem 92:525-33 CrossRef
    6. Day TF, Guo X, Garrett-Beal L, Yang Y (2005) Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell 8:739-50 CrossRef
    7. Favata MF, Horiuchi KY, Manos EJ, Daulerio AJ, Stradley DA, Feeser WS, Van Dyk DE, Pitts WJ, Earl RA, Hobbs F, Copeland RA, Magolda RL, Scherle PA, Trzaskos JM (1998) Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J Biol Chem 273:18623-8632 CrossRef
    8. Garrington TP, Johnson GL (1999) Organization and regulation of mitogen-activated protein kinase signaling pathways. Curr Opin Cell Biol 11:211-18 CrossRef
    9. Gaur T, Lengner CJ, Hovhannisyan H, Bhat RA, Bodine PVN, Komm BS, Javed A, van Wijnen AJ, Stein JL, Stein GS, Lian JB (2005) Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression. J Biol Chem 280:33132-3140 CrossRef
    10. George J, Kuboki Y, Miyata T (2006) Differentiation of mesenchymal stem cells into osteoblasts on honeycomb collagen scaffolds. Biotechnol Bioeng 95:404-11 CrossRef
    11. Golub EE, Harrison G, Taylor AG, Camper S, Shapiro IM (1992) The role of alkaline-phosphatase in cartilage mineralization. Bone Miner 17:273-78 CrossRef
    12. Guan M, Yao W, Liu R, Lam KS, Nolta J, Jia J, Panganiban B, Meng L, Zhou P, Shahnazari M, Ritchie RO, Lane NE (2012) Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass. Nat Med 18:456-62 CrossRef
    13. Higuchi C, Myoui A, Hashimoto N, Kuriyama K, Yoshioka K, Yoshikawa H, Itoh K (2002) Continuous inhibition of MAPK signaling promotes the early osteoblastic differentiation and mineralization of the extracellular matrix. J Bone Miner Res 17:1785-794 CrossRef
    14. Jackson RA, Kumarasuriyar A, Nurcombe V, Cool SM (2006) Long-term loading inhibits ERK1/2 phosphorylation and increases FGFR3 expression in MC3T3-E1 osteoblast cells. J Cell Physiol 209:894-04 CrossRef
    15. Jaiswal RK, Jaiswal N, Bruder SP, Mbalaviele G, Marshak DR, Pittenger MF (2000) Adult human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by mitogen-activated protein kinase. J Biol Chem 275:9645-652 Cross
  • 刊物类别:Biomedical and Life Sciences
  • 刊物主题:Biomedicine
    Human Genetics
    Proteomics
    Molecular Medicine
  • 出版者:Springer Berlin / Heidelberg
  • ISSN:1432-0878
文摘
U0126 has been reported as a specific inhibitor of the ERK1/2 signaling pathway, which plays a vital role during the osteogenic differentiation of mesenchymal stem cells (MSCs). We report the positive effect of U0126 on the osteogenesis of rat MSCs. We find that U0126 promotes the osteogenic differentiation of rat MSCs as demonstrated by the quantitative real-time polymerase chain reaction for osteogenic markers, alkaline phosphatase activity and calcium nodule formation. Our data indicate that U0126 enhances the BMP/Smad signaling pathway in rat MSCs, while inhibiting the ERK1/2 signaling pathway. Furthermore, Western blot results demonstrate that U0126 increases Smad1/5/8 phosphorylation synergistically with β-glycerophosphate. In addition, U0126 significantly increases the expression of BMP2 during the process of osteogenesis in rat MSCs and the level of phosphorylated Smad1/5/8 is significantly reduced by BMP2 antibody, suggesting that U0126 also promotes the expression of BMP2 to enhance Smad proteins phosphorylation. Thus, we demonstrate a novel function for U0126 in promoting osteogenic differentiation of rat MSCs by the activation of the BMP/Smad signaling pathway.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700