MiR-199a-5P promotes osteogenic differentiation of human stem cells from apical papilla via targeting IFIT2 in apical periodontitis

作者全名："Hu, Jing; Huang, Xia; Zheng, Liwen; Zhang, Yuxin; Zeng, Huan; Nie, Li; Pang, Xiaoxiao; Zhang, Hongmei"

作者地址："[Hu, Jing; Huang, Xia; Zheng, Liwen; Zhang, Yuxin; Zeng, Huan; Nie, Li; Pang, Xiaoxiao; Zhang, Hongmei] Chongqing Med Univ, Chongqing Key Lab Oral Dis & Biomed Sci, Affiliated Hosp Stomatol, Chongqing, Peoples R China; [Hu, Jing; Zheng, Liwen; Zhang, Yuxin; Zeng, Huan; Zhang, Hongmei] Chongqing Med Univ, Affiliated Stomatol Hosp, Dept Pediat Dent, Chongqing, Peoples R China; [Pang, Xiaoxiao] Chongqing Med Univ, Coll Stomatol, Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China"

通信作者："Pang, XX; Zhang, HM (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Oral Dis & Biomed Sci, Affiliated Hosp Stomatol, Chongqing, Peoples R China.; Zhang, HM (通讯作者)，Chongqing Med Univ, Affiliated Stomatol Hosp, Dept Pediat Dent, Chongqing, Peoples R China.; Pang, XX (通讯作者)，Chongqing Med Univ, Coll Stomatol, Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000967721400001

JCR分区：Q1

影响因子：7.3

年份：2023

卷号：14

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：apical periodontitis; microRNA; miR-199a-5p; human stem cells from apical papilla (hSCAPs); osteogenic differentiation; bone regeneration

摘要："IntroductionPeriapical alveolar bone loss is the common consequence of apical periodontitis (AP) caused by persistent local inflammation around the apical area. Human stem cells from apical papilla (hSCAPs) play a crucial role in the restoration of bone lesions during AP. Studies have recently identified the critical role of microRNAs (miRNAs) involved in AP pathogenesis, but little is known about their function and potential molecular mechanism, especially in the osteogenesis of hSCAPs during AP. Here, we investigated the role of clinical sample-based specific miRNAs in the osteogenesis of hSCAPs. MethodsDifferential expression of miRNAs were detected in the periapical tissues of normal and patients with AP via transcriptomic analysis, and the expression of miR-199a-5p was confirmed by qRT-PCR. Treatment of hSCAPs with miR-199a-5p mimics while loaded onto beta-tricalcium phosphate (beta-TCP) ceramic particle scaffold to explore its effect on osteogenesis in vivo. RNA binding protein immunoprecipitation (RIP) and Luciferase reporter assay were conducted to identify the target gene of miR-199a-5p. ResultsThe expression of miR-199a-5p was decreased in the periapical tissues of AP patients, and miR-199a-5p mimics markedly enhanced cell proliferation and osteogenic differentiation of hSCAPs, while miR-199a-5p antagomir dramatically attenuated hSCAPs osteogenesis. Moreover, we identified and confirmed Interferon Induced Protein with Tetratricopeptide Repeats 2 (IFIT2) as a specific target of miR-199a-5p, and silencing endogenous IFIT2 expression alleviated the inhibitory effect of miR-199a-5p antagomir on the osteogenic differentiation of hSCAPs. Furthermore, miR-199a-5p mimics transfected hSCAPs loaded onto beta-tricalcium phosphate (beta-TCP) scaffolds induced robust subcutaneous ectopic bone formation in vivo. DiscussionThese results strengthen our understanding of predictors and facilitators of the key AP miRNAs (miR-199a-5p) in bone lesion repair under periapical inflammatory conditions. And the regulatory networks will be instrumental in exploring the underlying mechanisms of AP and lay the foundation for future regenerative medicine based on dental mesenchymal stem cells."

基金机构："National Natural Science Foundation of China [81870758, 32000572]; Natural Science Foundation of Chongqing [cstc2021jcyjmsxmX0560]; Postdoctoral Project of Chongqing Natural Science Foundation [cstc2020jcyj-bshX0107]; China Postdoctoral Science Foundation [2020M683267]"

基金资助正文："Funding The reported work was supported in part by research grants from the National Natural Science Foundation of China (81870758 to HZ and 32000572 to XP), Natural Science Foundation of Chongqing (cstc2021jcyjmsxmX0560 to HZ), Postdoctoral Project of Chongqing Natural Science Foundation (cstc2020jcyj-bshX0107 to XP), and China Postdoctoral Science Foundation (2020M683267 to XP)."