Demethylation of SFRP2 by histone demethylase KDM2A regulated osteo‐/dentinogenic differentiation of stem cells of the apical papilla

Guoxia Yu; Jinsong Wang; Xiao Lin; Shu Diao; Yu Cao; Rui Dong; Liping Wang; Songlin Wang; Zhipeng Fan

doi:10.1111/cpr.12256

journal article Apr 13, 2016

Demethylation of SFRP2 by histone demethylase KDM2A regulated osteo‐/dentinogenic differentiation of stem cells of the apical papilla

Guoxia Yu Jinsong Wang

Shu Diao Yu Cao

Cell Proliferation Vol. 49 No. 3 pp. 330-340 · Wiley

View at Publisher Save 10.1111/cpr.12256

Abstract

AbstractObjectivesDental mesenchymal stem cells (MSCs) are easily obtained; however, mechanisms underlying directed differentiation of these cells remains unclear. Wnt/β‐catenin signalling is essential for mesenchymal cell commitment and differentiation, and Wnt inhibition is linked to stem cell maintenance and function. Secreted frizzled‐related protein 2 (SFRP2) competes with the Frizzled receptor for direct binding to Wnt and blocks activation of Wnt signalling. Here, we used stem cells derived from apical papillae (SCAPs) to study the functions of SFRP2.Materials and methodsSCAPs were isolated from apical papillae of immature third molars. The cells were analysed using alkaline phosphatase activity assays, Alizarin red staining and quantitative calcium measurements. In addition, we evaluated expression profile of genes associated with osteogenesis and dentinogenesis (osteo‐/dentinogenesis), and conducted in vivo transplantation experiments to determine osteo‐/dentinogenic differentiation potential of SCAPs. ChIP assays were used to detect histone methylation at the SFRP2 promoter.ResultsWe found that SFRP2 enhanced osteo‐/dentinogenic differentiation via Osterix, a key transcription factor in SCAPs. Furthermore, silencing SFRP2 induced SCAP cell death in osteogenic‐inducing medium, indicating that SFRP2 is a key factor in maintaining SCAP survival following osteo‐/dentinogenic commitment. Moreover, we found that silencing KDM2A, a histone demethylase and BCL6 co‐repressor, de‐repressed SFRP2 transcription by increasing histone H3K4 and H3K36 methylation at the SFRP2 promoter.ConclusionsOur results have identified a new function of SFRP2 and shed new light on the molecular mechanism underlying directed differentiation of stem cells of dental origin.

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References

Details

Published: Apr 13, 2016
Vol/Issue: 49(3)
Pages: 330-340
License: View

Authors

G

Guoxia Yu

Laboratory of Molecular Signaling and Stem Cells Therapy Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Capital Medical University School of Stomatology Beijing 100050 China; Molecular Laboratory for Gene Therapy and Tooth Regeneration Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Capital Medical University School of Stomatology Beijing 100050 China; Department of Stomatology Beijing Children's Hospital Capital Medical University Beijing 100045 China

J

Jinsong Wang

Molecular Laboratory for Gene Therapy and Tooth Regeneration Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Capital Medical University School of Stomatology Beijing 100050 China; Department of Biochemistry and Molecular Biology Capital Medical University School of Basic Medical Sciences Beijing 100069 China

X

Xiao Lin

Laboratory of Molecular Signaling and Stem Cells Therapy Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Capital Medical University School of Stomatology Beijing 100050 China; Department of Implant Dentistry Capital Medical University School of Stomatology Beijing 100050 China

S

Shu Diao

Laboratory of Molecular Signaling and Stem Cells Therapy Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Capital Medical University School of Stomatology Beijing 100050 China

Y

Yu Cao

Laboratory of Molecular Signaling and Stem Cells Therapy Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Capital Medical University School of Stomatology Beijing 100050 China; Molecular Laboratory for Gene Therapy and Tooth Regeneration Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Capital Medical University School of Stomatology Beijing 100050 China

R

Rui Dong

Laboratory of Molecular Signaling and Stem Cells Therapy Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Capital Medical University School of Stomatology Beijing 100050 China

L

Liping Wang

Laboratory of Molecular Signaling and Stem Cells Therapy Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Capital Medical University School of Stomatology Beijing 100050 China

S

Songlin Wang

Molecular Laboratory for Gene Therapy and Tooth Regeneration Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Capital Medical University School of Stomatology Beijing 100050 China; Department of Biochemistry and Molecular Biology Capital Medical University School of Basic Medical Sciences Beijing 100069 China

Z

Zhipeng Fan

Laboratory of Molecular Signaling and Stem Cells Therapy Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Capital Medical University School of Stomatology Beijing 100050 China

Funding

National Natural Science Foundation of China Award: 81271100

Natural Science Foundation of Beijing Municipality Award: 5132011

Program for New Century Excellent Talents in University Award: NCET‐12‐0611

Cite This Article

Guoxia Yu, Jinsong Wang, Xiao Lin, et al. (2016). Demethylation of SFRP2 by histone demethylase KDM2A regulated osteo‐/dentinogenic differentiation of stem cells of the apical papilla. Cell Proliferation, 49(3), 330-340. https://doi.org/10.1111/cpr.12256

Demethylation of SFRP2 by histone demethylase KDM2A regulated osteo‐/dentinogenic differentiation of stem cells of the apical papilla

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