SFRP2 enhances the osteogenic differentiation of apical papilla stem cells by antagonizing the canonical WNT pathway |
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| Authors: | Luyuan Jin Yu Cao Guoxia Yu Jinsong Wang Xiao Lin Lihua Ge Juan Du Liping Wang Shu Diao Xiaomeng Lian Songlin Wang Rui Dong Zhaochen Shan |
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| Institution: | 1.Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction,Capital Medical University School of Stomatology,Beijing,China;2.Department of Implant Dentistry,Capital Medical University School of Stomatology,Beijing,China;3.Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction,Capital Medical University School of Stomatology,Beijing,China;4.Department of Stomatology, Beijing Children’s Hospital,Capital Medical University,Beijing,China;5.Department of Biochemistry and Molecular Biology,Capital Medical University School of Basic Medical Sciences,Beijing,China;6.Department of Stomatology, Beijing Shijitan Hospital,Capital Medical University,Beijing,China;7.Oral and Maxillofacial Surgery Department,Capital Medical University School of Stomatology,Beijing,China |
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| Abstract: | BackgroundExploring 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.MethodsSCAPs 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.ConclusionsThe 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. |
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