CaSR as a Therapeutic Target and Tool in Human Dental Pulp: A Concise Review and Novel Hypothesis

Purpose: To review the essential characteristics of calcium sensing receptor (CaSR) and explore the hypothesis that elevated extracellular calcium ions (Ca2+) may affect the odontogenic/osteogenic differentiation and mineralisation of human dental pulp cells (hDPCs) through the CaSR signal. Materials and Methods: Based on a literature search of databases using different combinations of the key words and our previous researches, we gleaned the following important viewpoints. Results: The Ca2+ released from pulp capping materials plays an essential role in maintaining the viability and function of human dental pulp, and elevated extracellular Ca2+ concentrations can promote the odontogenic/osteogenic differentiation and mineralisation of hDPCs. Ca2+ is the primary physiological ligand of the CaSR, which has been reported to be widely expressed in a broad range of cells, including various osteoblast-like cell lines, osteoprogenitor cells, and mature osteoblasts. hDPCs consist of different subpopulations and have been shown to share phenotypical features with osteoblasts. Thus, we speculated that hDPCs also express CaSR and respond to extracellular Ca2+ via this receptor. Calcimimetics are indirect allosteric regulators of CaSR function and can increase the receptor's sensitivity to ambient Ca2+. Conclusion: The local use of calcimimetics and calcium-based pulp capping materials could create an option for promoting the Ca2+ influx of hDPCs from the extracellular space via the CaSR. Such elevated Ca2+ concentrations could enhance the odontogenic/osteogenic differentiation and mineralisation of hDPCs and eventually improve the success rate of direct pulp capping treatments in patients suffering from accidental dental pulp exposure. Keywords: calcium sensing receptor, calcimimetics, human dental pulp cells, osteogenic differentiation