SCAPs Regulate DFSC Differentiation via the Osteoglycin-Hedgehog Pathway

The developing root apical complex, including the Hertwig's epithelial root sheath, apical papilla, and dental follicle (DF), is the germinal center of root development wherein the DF constantly develops into periodontal tissues. However, whether the DF development is regulated by the adjacent apical papilla is largely unknown. In this study, using a transwell system in vitro, we found that stem cells from the apical papilla (SCAPs) inhibited the differentiation but maintained the stemness of dental follicle stem cells (DFSCs). Furthermore, high-throughput transcriptome sequencing revealed that the Hedgehog (Hh) pathways were significantly downregulated in DFSCs when co-cultured with SCAPs. Upregulation or downregulation of the Hh pathway could activate or inhibit the multidirectional differentiation of DFSCs, respectively. By secreting osteoglycin (OGN), the SCAPs regulated the stemness and multidirectional differentiation of DFSCs via the OGN-Hh pathway. Overall design: Comparative gene expression profiling analysis of RNA-seq data for dental follicle (DF)/Co-culture DFSCs/Control DFSCs