Ji Fang, Zhu Lanying, Pan Jing, Shen Zhecheng, Yang Zhao, Wang Jian, Bai Xuebing, Lin Yueting, Tao Jiang
Department of Orthodontics, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China.
Front Cell Dev Biol. 2020 Jun 26;8:470. doi: 10.3389/fcell.2020.00470. eCollection 2020.
Previous studies have found that circular RNA (circRNA) hsa_circ_0026827 plays a role during osteoblast differentiation, but the mechanism is unclear. The aim of this study was to illuminate the role of hsa_circ_0026827 in human dental pulp stem cells (DPSCs) during osteoblast differentiation. The results show that hsa_circ_0026827 expression significantly increased during osteoblast differentiation, while knockdown of hsa_circ_0026827 suppressed DPSC-derived osteoblast differentiation. microRNA (miRNA) expression profile analysis showed that downregulation of hsa_circ_0026827 promoted miR-188-3p expression. miR-188-3p downregulation restored osteogenic differentiation of DPSCs after hsa_circ_0026827 was silenced. Luciferase reporter assays verified that miR-188-3p was the target of hsa_circ_0026827 and also demonstrated that Beclin1 and RUNX1 were miR-188-3p downstream targets. miR-188-3p overexpression suppressed DPSC osteogenic differentiation by targeting Beclin-1-mediated autophagy and runt-related transcription factor 1 (RUNX1). studies using a heterotopic bone model also found that hsa_circ_0026827 overexpression plays an important role in promoting heterotopic bone formation. In conclusion, our research indicates that hsa_circ_0026827 promotes osteoblast differentiation of DPSCs via Beclin1 and the RUNX1 signaling pathways by sponging miR-188-3p, which suggests novel therapeutics for osteoporosis treatment.
先前的研究发现，环状RNA（circRNA）hsa_circ_0026827在成骨细胞分化过程中发挥作用，但其机制尚不清楚。本研究的目的是阐明hsa_circ_0026827在人牙髓干细胞（DPSC）成骨细胞分化过程中的作用。结果表明，hsa_circ_0026827的表达在成骨细胞分化过程中显著增加，而敲低hsa_circ_0026827可抑制DPSC来源的成骨细胞分化。微小RNA（miRNA）表达谱分析表明，hsa_circ_0026827的下调促进了miR-188-3p的表达。在hsa_circ_0026827沉默后，miR-188-3p的下调恢复了DPSC的成骨分化。荧光素酶报告基因检测证实miR-188-3p是hsa_circ_0026827的靶标，同时也证明Beclin1和RUNX1是miR-188-3p的下游靶标。miR-188-3p的过表达通过靶向Beclin-1介导的自噬和 runt相关转录因子1（RUNX1）抑制DPSC的成骨分化。使用异位骨模型的研究还发现，hsa_circ_0026827的过表达在促进异位骨形成中起重要作用。总之，我们的研究表明，hsa_circ_0026827通过海绵化miR-188-3p，经由Beclin1和RUNX1信号通路促进DPSC的成骨细胞分化，这为骨质疏松症的治疗提供了新的治疗方法。
