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SFRP2 enhances the osteogenic differentiation of apical papilla stem cells by antagonizing the canonical WNT pathway
BACKGROUND: Exploring the molecular mechanisms underlying directed differentiation is helpful in the development of clinical applications of mesenchymal stem cells (MSCs). Our previous study on dental tissue-derived MSCs demonstrated that secreted frizzled-related protein 2 (SFRP2), a Wnt inhibitor,...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547503/ https://www.ncbi.nlm.nih.gov/pubmed/28794794 http://dx.doi.org/10.1186/s11658-017-0044-2 |
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author | Jin, Luyuan Cao, Yu Yu, Guoxia Wang, Jinsong Lin, Xiao Ge, Lihua Du, Juan Wang, Liping Diao, Shu Lian, Xiaomeng Wang, Songlin Dong, Rui Shan, Zhaochen |
author_facet | Jin, Luyuan Cao, Yu Yu, Guoxia Wang, Jinsong Lin, Xiao Ge, Lihua Du, Juan Wang, Liping Diao, Shu Lian, Xiaomeng Wang, Songlin Dong, Rui Shan, Zhaochen |
author_sort | Jin, Luyuan |
collection | PubMed |
description | BACKGROUND: Exploring the molecular mechanisms underlying directed differentiation is helpful in the development of clinical applications of mesenchymal stem cells (MSCs). Our previous study on dental tissue-derived MSCs demonstrated that secreted frizzled-related protein 2 (SFRP2), a Wnt inhibitor, could enhance osteogenic differentiation in stem cells from the apical papilla (SCAPs). However, how SFRP2 promotes osteogenic differentiation of dental tissue-derived MSCs remains unclear. In this study, we used SCAPs to investigate the underlying mechanisms. METHODS: SCAPs were isolated from the apical papilla of immature third molars. Western blot and real-time RT-PCR were applied to detect the expression of β-catenin and Wnt target genes. Alizarin Red staining, quantitative calcium analysis, transwell cultures and in vivo transplantation experiments were used to study the osteogenic differentiation potential of SCAPs. RESULTS: SFRP2 inhibited canonical Wnt signaling by enhancing phosphorylation and decreasing the expression of nuclear β-catenin in vitro and in vivo. In addition, the target genes of the Wnt signaling pathway, AXIN2 (axin-related protein 2) and MMP7 (matrix metalloproteinase-7), were downregulated by SFRP2. WNT1 inhibited the osteogenic differentiation potential of SCAPs. SFRP2 could rescue this WNT1-impaired osteogenic differentiation potential. CONCLUSIONS: The results suggest that SFRP2 could bind to locally present Wnt ligands and alter the balance of intracellular Wnt signaling to antagonize the canonical Wnt pathway in SCAPs. This elucidates the molecular mechanism underlying the SFRP2-mediated directed differentiation of SCAPs and indicates potential target genes for improving dental tissue regeneration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s11658-017-0044-2) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5547503 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-55475032017-08-09 SFRP2 enhances the osteogenic differentiation of apical papilla stem cells by antagonizing the canonical WNT pathway Jin, Luyuan Cao, Yu Yu, Guoxia Wang, Jinsong Lin, Xiao Ge, Lihua Du, Juan Wang, Liping Diao, Shu Lian, Xiaomeng Wang, Songlin Dong, Rui Shan, Zhaochen Cell Mol Biol Lett Research BACKGROUND: Exploring the molecular mechanisms underlying directed differentiation is helpful in the development of clinical applications of mesenchymal stem cells (MSCs). Our previous study on dental tissue-derived MSCs demonstrated that secreted frizzled-related protein 2 (SFRP2), a Wnt inhibitor, could enhance osteogenic differentiation in stem cells from the apical papilla (SCAPs). However, how SFRP2 promotes osteogenic differentiation of dental tissue-derived MSCs remains unclear. In this study, we used SCAPs to investigate the underlying mechanisms. METHODS: SCAPs were isolated from the apical papilla of immature third molars. Western blot and real-time RT-PCR were applied to detect the expression of β-catenin and Wnt target genes. Alizarin Red staining, quantitative calcium analysis, transwell cultures and in vivo transplantation experiments were used to study the osteogenic differentiation potential of SCAPs. RESULTS: SFRP2 inhibited canonical Wnt signaling by enhancing phosphorylation and decreasing the expression of nuclear β-catenin in vitro and in vivo. In addition, the target genes of the Wnt signaling pathway, AXIN2 (axin-related protein 2) and MMP7 (matrix metalloproteinase-7), were downregulated by SFRP2. WNT1 inhibited the osteogenic differentiation potential of SCAPs. SFRP2 could rescue this WNT1-impaired osteogenic differentiation potential. CONCLUSIONS: The results suggest that SFRP2 could bind to locally present Wnt ligands and alter the balance of intracellular Wnt signaling to antagonize the canonical Wnt pathway in SCAPs. This elucidates the molecular mechanism underlying the SFRP2-mediated directed differentiation of SCAPs and indicates potential target genes for improving dental tissue regeneration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s11658-017-0044-2) contains supplementary material, which is available to authorized users. BioMed Central 2017-08-08 /pmc/articles/PMC5547503/ /pubmed/28794794 http://dx.doi.org/10.1186/s11658-017-0044-2 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Jin, Luyuan Cao, Yu Yu, Guoxia Wang, Jinsong Lin, Xiao Ge, Lihua Du, Juan Wang, Liping Diao, Shu Lian, Xiaomeng Wang, Songlin Dong, Rui Shan, Zhaochen SFRP2 enhances the osteogenic differentiation of apical papilla stem cells by antagonizing the canonical WNT pathway |
title | SFRP2 enhances the osteogenic differentiation of apical papilla stem cells by antagonizing the canonical WNT pathway |
title_full | SFRP2 enhances the osteogenic differentiation of apical papilla stem cells by antagonizing the canonical WNT pathway |
title_fullStr | SFRP2 enhances the osteogenic differentiation of apical papilla stem cells by antagonizing the canonical WNT pathway |
title_full_unstemmed | SFRP2 enhances the osteogenic differentiation of apical papilla stem cells by antagonizing the canonical WNT pathway |
title_short | SFRP2 enhances the osteogenic differentiation of apical papilla stem cells by antagonizing the canonical WNT pathway |
title_sort | sfrp2 enhances the osteogenic differentiation of apical papilla stem cells by antagonizing the canonical wnt pathway |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547503/ https://www.ncbi.nlm.nih.gov/pubmed/28794794 http://dx.doi.org/10.1186/s11658-017-0044-2 |
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