Ror Alpha Regulates Odontoblastic Differentiation And Mediates The Pro-Odontogenic Effect Of Melatonin On Dental Papilla Cells

Dental papilla cells (DPCs), precursors of odontoblasts, are considered promising seed cells for tissue engineering. Emerging evidence suggests that melatonin promotes odontoblastic differentiation of DPCs and affects tooth development, although the precise mechanisms remain unknown. Retinoid acid receptor-related orphan receptor alpha (ROR alpha) is a nuclear receptor for melatonin that plays a critical role in cell differentiation and embryonic development. This study aimed to explore the role of ROR alpha in odontoblastic differentiation and determine whether melatonin exerts its pro-odontogenic effect via ROR alpha. Herein, we observed that ROR alpha was expressed in DPCs and was significantly increased during odontoblastic differentiation in vitro and in vivo. The overexpression of ROR alpha upregulated the expression of odontogenic markers, alkaline phosphatase (ALP) activity and mineralized nodules formation (p < 0.05). In contrast, odontoblastic differentiation of DPCs was suppressed by ROR alpha knockdown. Moreover, we found that melatonin elevated the expression of odontogenic markers, which was accompanied by the upregulation of ROR alpha (p < 0.001). Utilising small interfering RNA, we further demonstrated that ROR alpha inhibition attenuated melatonin-induced odontogenic gene expression, ALP activity and matrix mineralisation (p < 0.01). Collectively, these results provide the first evidence that ROR alpha can promote odontoblastic differentiation of DPCs and mediate the pro-odontogenic effect of melatonin.