Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.
Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510080, China.
Molecules. 2021 Feb 19;26(4):1098. doi: 10.3390/molecules26041098.
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 ( < 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 ( < 0.001). Utilising small interfering RNA, we further demonstrated that RORα inhibition attenuated melatonin-induced odontogenic gene expression, ALP activity and matrix mineralisation ( < 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.
牙髓细胞（DPCs）是成牙本质细胞的前体细胞，被认为是组织工程有前途的种子细胞。新出现的证据表明，褪黑素促进 DPCs 的成牙本质分化，并影响牙齿发育，尽管确切的机制尚不清楚。视黄酸受体相关孤儿受体α（RORα）是褪黑素的核受体，在细胞分化和胚胎发育中起关键作用。本研究旨在探讨 RORα 在成牙本质分化中的作用，并确定褪黑素是否通过 RORα 发挥其促牙源性作用。在此，我们观察到 RORα 在 DPCs 中表达，并在体外和体内成牙本质分化过程中显著增加。RORα 的过表达上调了牙源性标志物、碱性磷酸酶（ALP）活性和矿化结节形成的表达（<0.05）。相反，RORα 敲低抑制了 DPCs 的成牙本质分化。此外，我们发现褪黑素上调了牙源性标志物的表达，同时 RORα 的表达也上调（<0.001）。利用小干扰 RNA，我们进一步证明 RORα 抑制减弱了褪黑素诱导的牙源性基因表达、ALP 活性和基质矿化（<0.01）。总之，这些结果首次表明 RORα 可以促进 DPCs 的成牙本质分化，并介导褪黑素的促牙源性作用。
