Fig 2: KDM2B was the downstream target of miR-206. a Heatmap of differentially expressed miRNAs in tooth germ co-cultured with mandible-EVs. b Volcano plot filtering of differentially expressed miRNAs. c The level of miR-206 in co-cultured dental mesenchymal cells. d The level of miR-206 in mandible-EVs. e, f Luciferase reporter designing. g Transfection of miR-206 mimics with luciferase reporter. h The mRNA level of KDM2B regulated by miR-206. n.s not significant, * P < 0.05, ** P < 0.01

Fig 3: MiR-206/KDM2B regulated early tooth development in vivo. a Morphological characteristics under a stereomicroscope. Scale bar: 1 mm. b Schematic of the method for measuring tooth morphology. c The cusp height of tooth. d The height of tooth. e The width of tooth. f Three-dimensional reconstruction of micro-CT images. Scale bar: 1 mm. g, h Quantification analyses of MV/TV, and Mineral density. MV/TV, mineral volume/tissue volume; The enamel and dentin density ranges were defined as (1.19 ± 0.10) g/cm3 and (0.68 ± 0.09) g/cm3; ** P < 0.01; n = 3

Fig 4: KDM2B was the downstream target of mandible-EVs during tooth development. a Heatmap of differentially expressed proteins in tooth germs co-cultured with mandible-EVs. b Gene Ontology (GO) analysis of proteins differentially expressed from tooth germs co-cultured with mandible-EVs. c Volcano plot filtering of differentially expressed proteins. d The level of KDM2B and H3K4me3 in dental mesenchymal cells co-cultured with mandible-EVs. e, f Western blotting quantification. g The enrichment of H3K4me3 at the promoter region of DSPP regulated by mandible-EVs. h The enrichment of H3K4me3 at the promoter region of DMP1 regulated by mandible-EVs. i EdU assays were applied to confirm the proliferation ability of dental mesenchymal cells. Scale bar: 200 μm. j Quantitative analysis. k The protein level of DSPP and DMP1 in dental mesenchymal cells treated with KDM2B. l, m Western blotting quantification. n.s not significant, * P < 0.05, ** P < 0.01