Pluripotency of periodontal ligament and dental pulp cells is induced by intercellular communication via the CDX2/Oct-4/Sox2 pathway

Abstract

Background: Intercellular communication in the environments of mature or aged cells can restore and regenerate their function and promote the expression of pluripotency markers. The regeneration of dental tissue is stimulated by periodontal ligament cells (PDLCs) and dental pulp cells (DPCs). However, the communication networks between the cells and their microenvironments are poorly understood.Methods: In this study, gene expression was analyzed by polymerase chain reaction, and chromatin immunoprecipitation assays, dual-luciferase assays, and electrophoretic mobility shift assays were used to analyze the signaling pathways associated with pluripotency after the knockdown or overexpression of caudal-type homeobox transcription factor 2 (CDX2).Results: Elevated levels of SRY-box transcription factor 2 (Sox2) and octamer-binding transcription factor 4 (Oct-4) were observed in the co-culture system, while the levels of CDX2 were significantly reduced. The overexpression of CDX2 promoted cell apoptosis and reduced the synthesis stage of the cell cycle. CDX2 was shown to bind directly to the promoter regions of Sox2 and Oct-4. The silencing of CDX2 promoted calcium deposition, adipogenic differentiation, and elevated alkaline phosphatase (ALP) activity in the DPCs.Conclusions: These findings demonstrate the enhancement of DPC and PDLC pluripotency by intercellular communication. CDX2 plays a significant part in the regulation of DPC and PDLC pluripotency via its regulation of Oct-4 and Sox2 expression.