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

组蛋白去甲基化酶 KDM2A 对 SFRP2 的去甲基化调节根尖乳头干细胞的骨/牙本质形成分化

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作者:Guoxia Yu, Jinsong Wang, Xiao Lin, Shu Diao, Yu Cao, Rui Dong, Liping Wang, Songlin Wang, Zhipeng Fan

Conclusions

Our 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.

Methods

SCAPs 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.

Results

We 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. Conclusions: Our 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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