Adenosine receptors enhance the ATP-induced odontoblastic differentiation of human dental pulp cells

Highlights: • ATP (600 μM) could induce the odontoblastic differentiation of HDPCs in vitro. • All four adenosine receptor subtypes were expressed in HDPCs. • Adenosine receptors were activated when HDPCs were treated with ATP. • A₁R and A_2BR played a positive role in ATP-induced HDPC odontoblastic differentiation. Purinergic signaling regulates various biological processes through the activation of adenosine receptors (ARs) and P2 receptors. ATP induces the odontoblastic differentiation of human dental pulp cells (HDPCs) via P2 receptors. However, there is no information available about the roles of ARs in HDPC odontoblastic differentiation induced by ATP. Here, we found that HDPCs treated with ATP showed higher activity of ADORA1 (A₁R), ADORA2B (A_2BR), and ADORA3 (A₃R). Inhibition of A₁R and A_2BR attenuated ATP-induced odontoblastic differentiation of HDPCs, whereas activation of the two receptors enhanced the odontoblastic differentiation induced by ATP. However, activation of ARs by adenosine did not induce the odontoblastic differentiation of HDPCs independently without induction of ATP. Our study indicates a positive role for ARs in ATP-induced odontoblastic differentiation of HDPCs, and demonstrates that ATP-induced odontoblastic differentiation of HDPCs may be due to the combined administration of ARs and P2 receptors. This study provides new insights into the molecular mechanisms of pulpal injury repair induced by ATP.