Secreted frizzled-related protein 2 promotes the osteo/odontogenic differentiation and paracrine potentials of stem cells from apical papilla under inflammation and hypoxia conditions

Objectives Mesenchymal stem cell (MSC)-based dental tissue regeneration is a potential treatment method in future, while inflammation and hypoxia niche will affect MSC-mediated tissue regeneration. In this research, we intended to investigate the influence and mechanism of secreted frizzled-related protein 2(SFRP2) on MSC function under inflammation and hypoxia conditions. Material and methods Stem cells from apical papilla (SCAPs) were used in this study. The alkaline phosphatase (ALP) activity, Alizarin Red S staining, scratch-simulated wound migration and transwell chemotaxis assay were used to evaluate the functions of SFRP2. The Western blot, real-time RT-PCR and ChIP assays were used to evaluate the mechanism of SFRP2. Results Under inflammation and hypoxia conditions, the over-expression of SFRP2 could enhance the osteo/odontogenic differentiation ability. Mechanismly, SFRP2 inhibited canonical Wnt/beta-catenin signalling pathway and then inhibited the target genes of nuclear factor kappa B (NFkB) signalling pathway. Inflammation or hypoxia conditions could promote the expression of lysine demethylase 2A (KDM2A) and repress SFRP2 transcription through decreasing histone methylation in the SFRP2 promoter. Besides, proteomic analysis showed that SFRP2 promoted SCAPs to secret more functional cytokines, which improve the migration, chemotaxis and osteo/odontogenic ability of MSCs. Conclusions Our discoveries revealed that SFRP2 enhanced the osteo/odontogenic differentiation and paracrine potentials of SCAPs under hypoxia and inflammation conditions and provided a potential cytokine for promoting tissue regeneration in hypoxia and inflammatory niche.