Dental regenerative therapy targeting sphingosine-1-phosphate (S1P) signaling pathway in endodontics

Abstract

The establishment of regenerative therapy in endodontics targeting the dentin-pulp complex, cementum, periodontal ligament tissue, and alveolar bone will provide valuable information to preserve teeth. It is well known that the application of stem cells such as induced pluripotent stem cells, embryonic stem cells, and somatic stem cells is effective in regenerative medicine. There are many somatic stem cells in teeth and periodontal tissues including dental pulp stem cells (DPSCs), stem cells from the apical papilla, and periodontal ligament stem cells. Particularly, several studies have reported the regeneration of clinical pulp tissue and alveolar bone by DPSCs transplantation. However, further scientific issues for practical implementation remain to be addressed. Sphingosine-1-phosphate (S1P) acts as a bioactive signaling molecule that has multiple biological functions including cellular differentiation, and has been shown to be responsible for bone resorption and formation. Here we discuss a strategy for bone regeneration and a possibility for regenerative endodontics targeting S1P signaling pathway as one of approaches for induction of regeneration by improving the regenerative capacity of endogenous cells. Scientific field of dental science Endodontology

Sphingosine-1-phosphate hinders the osteogenic differentiation of dental pulp stem cells in association with AKT signaling pathways

“…Indeed, S1P is known to control the shifting of osteoclast precursors from the bloodstream into bone marrow cavities via its receptor pathways. 42 Furthermore, other prior studies have reported that S1P regulates bone regeneration by enhancing the osteogenic differentiation of osteoblast-like cells 26 , 27 , 40 , 43 and also that this factor promotes osseous tissue growth in vivo. 28 , 29 The reason for this difference is not known but we speculate that one explanation may be a differential response to S1P between pulp stem cells and cell lines/primary human femoral head osteoblastic cells.…”

Role of Sphingosine-1-Phosphate in Human Dental Pulp Cells to Form Hard Tissue

“…S1PR1-3, are widely expressed in normal organisms, and a similar trend was observed in hDPCs. In particular, studies have highlighted the involvement of S1PR1 and S1PR2 in hard tissue formation in the alveolar bone [15][16][17] . These receptors are considered to play a significant role in the formation of bone and hard tissues, implying their crucial involvement in hard tissue formation in the dental pulp.…”

“…Additionally, S1P activates bone differentiation signals and enhances bone regeneration by regulating differentiation factors against apical periodontitis-induced apical periodontal tissue destruction. Matsuzaki et al reported that S1PR1 and 2 in the five isotypes of S1P receptors are highly expressed in osteoblasts exhibiting osteoblast differentiation and bone formation-promoting effects [15][16][17] . Thus, the relationship between S1P and its receptors has been exploited for the treatment of diseases.…”