Sphingosine-1-phosphate receptor 1-mediated odontogenic differentiation of mouse apical papilla-derived stem cells

Sphingosine-1-phosphate (S1P) exhibits receptor-mediated physiological effects by facilitating the differentiation of mesenchymal stem cells toward the osteoblast lineage. This study aimed to determine the effect of S1P on odontogenic differentiation of mouse immortalized stem cells of dental apical papilla (iSCAP) and assess the distribution of the S1P receptor 1 (S1PR1) in the apical papilla and the root canal wall of immature rat molars.

Immunostaining for S1PR1 was conducted at the apex of the rat mandibular first molar and within the root canal wall. The iSCAP was treated with S1P and bone morphogenetic protein (BMP)-9 (for comparison), and the expression levels of the odontogenic differentiation marker were evaluated via real-time reverse-transcriptase quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Mineralization and lipid droplet formation were evaluated via Alizarin red and Oil red O staining.

S1PR1-positive cells were expressed in areas of both apical papilla and dentin-pulp interface of root canal wall. During the odontogenic differentiation of iSCAP, S1P and BMP-9 increased the expression of the differentiation marker mRNA and secreted proteins including dentin sialophosphoprotein, dentin matrix phosphoprotein 1, and matrix extracellular phosphoglycoprotein. The S1PR1 signaling pathway is involved in the action of S1P, but not that of BMP-9. S1PR1 signaling also facilitated mineralization in iSCAP and suppressed the differentiation of these cells into adipocytes.

S1P induced odontogenic differentiation of iSCAP through S1PR1. Furthermore, S1PR1-positive cells were expressed in the apical papilla of immature rat molars and in the dentin-pulp interface where odontoblast-like cells exist.