Abstract
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 α (RORα) 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 RORα in odontoblastic differentiation and determine whether melatonin exerts its pro-odontogenic effect via RORα. Herein, we observed that RORα was expressed in DPCs and was significantly increased during odontoblastic differentiation in vitro and in vivo. The overexpression of RORα 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 RORα knockdown. Moreover, we found that melatonin elevated the expression of odontogenic markers, which was accompanied by the upregulation of RORα (p < 0.001). Utilising small interfering RNA, we further demonstrated that RORα inhibition attenuated melatonin-induced odontogenic gene expression, ALP activity and matrix mineralisation (p < 0.01). Collectively, these results provide the first evidence that RORα can promote odontoblastic differentiation of DPCs and mediate the pro-odontogenic effect of melatonin.
Highlights
Oral diseases such as dental caries, pulp and periodontal diseases, dental trauma and tooth loss are major public health problems worldwide, affecting the general health and quality of life of individuals [1]
RT-PCR data performed reverse transcription polymerase chain reaction (RT-PCR) and agarose gel revealed that receptor α (RORα) and RORβ, but not RORγ, were expressed in rat dental papilla cells (rDPCs); the electrophoresis assay using specific primers for RORα, RORβ, and RORγ
dentin matrix protein 1 (DMP1), and alkaline phosphatase (ALP) were notably downregulated in the RORα knockdown group
Summary
Oral diseases such as dental caries, pulp and periodontal diseases, dental trauma and tooth loss are major public health problems worldwide, affecting the general health and quality of life of individuals [1]. Conventional treatments are widely used in clinical practice, including root canal therapy, dental prostheses, and implants; these techniques cannot completely recover pulp vitality and tooth function. The promising therapeutic strategy of regenerative medicine is gaining much attention for oral diseases because they can repair or regenerate various damaged dental tissues [2,3]. To facilitate the application of dental regeneration, it is essential to understand the process of tooth development. Dental papilla cells (DPCs), derived from the cranial neural crest, are precursors of odontoblasts and are responsible for dentinogenesis; they play an indispensable role in tooth development [4,5,6]. When the root is incompletely formed, dental papilla residing in the apical zone is called the apical papilla, which still contains a number of mesenchymal stem cells [8]
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