Circ_015350 Mediates Odonto/osteogenic Differentiation in Different Stem Cells

Bone marrow stem cells (BMSCs), dental pulp stem cells (DPSCs), and periodontal ligament stem cells (PDLSCs) represent key stem cell sources for regenerative endodontic therapy. Recent studies indicate that these 3 cell types exhibit similar mineralization potential during mineralized induction. This study aimed to compare the mineralization potential (including odontogenic and osteogenic potential) of these 3 mouse-derived cells and identify shared or related circular RNA-mediated regulatory mechanisms. In this study, we observed high expression levels of osteogenic differentiation markers alkaline phosphatase (ALP), RUNX2, and osteocalcin (OCN) in both BMSCs and PDLSCs during mineralization, while key markers for odontoblastic differentiation (DSPP and DMP-1) were significantly upregulated, specifically in DPSCs. Bioinformatics and experimental validation identified circ_015350 as consistently upregulated during mineralization. Functional studies demonstrated that circ_015350 knockdown reduced mineralization markers: ALP and OCN in BMSCs/PDLSCs, while primarily affecting DMP-1 and DSPP in DPSCs. Conversely, circ_015350 overexpression enhanced odonto/osteogenic markers across all cell types, with particularly strong DMP-1 and DSPP elevation in DPSCs. Bioinformatics analysis predicted circ_015350 interactions with 10 microRNAs and 89 RNA-binding proteins, along with involvement in Hippo, PI3K-Akt, and AMPK pathways. Our findings reveal distinct differentiation potential: BMSCs showed greater osteogenic capacity, while DPSCs displayed stronger odontogenic potential. Circ_015350 emerged as a key regulator promoting both odontogenic and osteogenic differentiation in all 3 stem cell types, with particularly pronounced effects on odontogenic differentiation. These results suggest circ_015350 as a potential therapeutic target for dental tissue regeneration, although further investigation is needed to fully elucidate its downstream regulatory mechanisms.