CircRNA-SNX13通过hsa-let-7b/COL1A1影响根尖牙乳头干细胞生物学特性的机制研究

Pulpal and periapical diseases are common oral diseases which usually cause infection and necrosis of pulp, even tooth loss. Stem cells from apical papilla (SCAPs) are closely associated with pulp and tooth root development，thus could be used in pulp regeneration to provide a new therapeutic approach for the pulp and periapical diseases. Our previous study has revealed that CircRNA-SNX13 was significantly up-regulated in the osteogenic differentiation of SCAPs, while the bioinformatics analysis has predicted the binding sites between CircRNA-SNX13 and hsa-let-7b, hsa-let-7b and COL1A1. After the deletion of CircRNA-SNX13, we observed the down-regulation of osteogenic differentiation in SCAPs. Thus, we propose that CircRNA-SNX13 might function as a competitive endogenous RNA to regulate COL1A1 expression by sponging hsa-let-7b in regulating the biological characteristics of SCAPs. Cell biological characteristics, molecular biological mechanism, and cell transplantation in vivo will be explored for the hypothesis verification. These upcoming results will be helpful to reveal the molecular mechanism during the proliferation, migration, and odonto/osteogenic differentiation of SCAPs, thus will afford theoretical support for the pulp regeneration.

牙髓根尖周病是口腔常见疾病，常导致牙髓感染坏死甚至牙丧失。根尖牙乳头干细胞（SCAPs）和牙髓、根尖发育密切相关, 运用组织工程技术将其应用于牙髓根尖周病的治疗, 促进牙髓再生有望成为新的治疗途径。我们前期研究发现CircRNA-SNX13在矿化诱导的SCAPs中显著高表达, 生物信息学预测CircRNA-SNX13与hsa-let-7b，hsa-let-7b与COL1A1有结合位点。低表达CircRNA-SNX13后，SCAPs的骨向分化能力减弱。因此我们假设CircRNA-SNX13通过hsa-let-7b/COL1A1轴调控SCAPs生物学特性，并拟从细胞生物学特性、分子生物学机制和动物体内移植三个层面进行验证，以期阐明CircRNA-SNX13/hsa-let-7b/COL1A1轴调控SCAPs增殖、迁移和牙/骨向分化的作用机制，为基于SCAPs的牙髓再生研究提供理论依据。

牙髓根尖周病是影响口腔健康的常见病,多发病,常引起剧烈疼痛和牙髓感染坏死。探讨根尖牙乳头干细胞增殖、迁移和牙/骨向分化等生物学进程中的重要分子调控机制,以促进牙髓组织的修复再生,是本课题将探讨的重要科学问题。本研究旨在探索CircRNA-SNX13在调控根尖牙乳头干细胞（SCAPs）生物学进程中的作用。CircRNA-SNX13对SCAPs增殖能力无影响。CircRNA-SNX13可促进SCAPs成骨向分化。Hsa-let-7b可抑制SCAPs成骨向分化，COL1A1可促进SCAPs的成骨向分化。通过生物学信息学分析以及双荧光素酶报告基因实验验证CircRNA-SNX13与hsa-let-7b存在结合位点, COL1A1是hsa-let-7b的直接靶点。此外,通过挽救实验显示下调hsa-let-7b表达可以挽救CircRNA-SNX13低表达对SCAPs成骨的抑制作用。本研究揭示CircRNA-SNX13通过调控hsa-let-7b/COL1A1轴促进SCAPs的成骨向分化。本课题的研究成果,有助于揭示 CircRNA-SNX13 通过 hsa-let-7b/COL1A1 轴调控根尖牙乳头干细胞生物学特性的分子机制,为根尖牙乳头干细胞的功能改建提供实验依据,为其介导的牙髓组织再生及临床转化研究奠定理论基础。