Circular RNA SIPA1L1 regulates osteoblastic differentiation of stem cells from apical papilla via miR-204-5p/ALPL pathwa
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RESEARCH
Open Access
Circular RNA SIPA1L1 regulates osteoblastic differentiation of stem cells from apical papilla via miR-204-5p/ALPL pathway Yuzhi Li1,2†, Minxia Bian1,2†, Zhou Zhou1,2†, Xiao Wu1,2, Xingyun Ge1, Tong Xiao1,2 and Jinhua Yu1,2*
Abstract Background: Osteogenesis is a complex biological process which requires the coordination of multiple molecular mechanisms. This research aimed to explore the biological role and underlying regulatory mechanism of circSIPA1L1 during the osteogenic differentiation of stem cells from apical papilla (SCAPs). Methods: EdU retention assay, flow cytometry assay, and CCK-8 assay were used to evaluate the proliferation capacity of SCAPs. Western blot assay, alkaline phosphatase (ALP), and alizarin red staining (ARS) were conducted to investigate the biological roles of circSIPA1L1 and miR-204-5p. Fluorescence in situ hybridization was applied for circSIPA1L1 localization. Dual-luciferase reporter assay was performed to prove the interaction of circSIPA1L1 and miR-204-5p. Results: CircSIPA1L1 had no significant effect on the proliferative capacity of SCAPs. CircSIPA1L1 promotes osteogenic differentiation of SCAPs by serving as a miRNA sponge for miR-204-5p. Either knockdown of circSIPA1L1 or overexpression of miR-204-5p significantly suppresses osteogenic differentiation of SCAPs. Conclusions: CircSIPA1L1 upregulates ALPL through targeting miR-204-5p and promotes the osteogenic differentiation of SCAPs. Keywords: circRNAs, miR-204-5p, ALPL, SCAPs, Differentiation
Background Cell-based tissue regeneration gives the field of regenerative medicine a boost. Mesenchymal stem cells (MSCs) present their superiority in individual treatment of tissue engineering based on their self-renew and multi-differentiation ability. They can differentiate into a variety of cell types such as osteocytes, chondrocytes, and adipocytes [1, 2]. As promising mesenchymal stem cells, SCAPs are isolated from human immature impacted permanent teeth, their essential roles in the * Correspondence: [email protected] † Yuzhi Li, Minxia Bian and Zhou Zhou contributed equally to this work. 1 Key Laboratory of Oral Diseases of Jiangsu Province and Stomatological Institute of Nanjing Medical University, 136 Hanzhong Road, Nanjing 210029, Jiangsu, China 2 Endodontic Department, School of Stomatology, Nanjing Medical University, Nanjing, Jiangsu, China
dental pulp and dentin formation, alveolar bone regeneration, and tooth root growth have been extensively studied [3]. Increasing evidences have demonstrated that SCAPs could exhibit advantages of proliferative capacity and differentiation ability such as adipogenic, osteogenic, and neurogenic [4, 5]. Besides, many previous studies have indicated the bone tissue formation and regeneration capacities of SCAPs [6–8]. Circular RNAs (circRNAs) are a class of naturally occurring non-coding RNAs, which are abundant in the eukaryotic transcriptome and involve in regulating physiological processes [2, 9, 10]. Compared with traditional linear RNAs, circRNA molecules h
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