Notch signaling regulates mineralization via microRNA modulation in dental pulp stem cells.

IF 2.9 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
Oral diseases Pub Date : 2024-10-01 Epub Date: 2024-01-19 DOI:10.1111/odi.14868
Promphakkon Kulthanaamondhita, Chatvadee Kornsuthisopon, Ajjima Chansaenroj, Ravipha Suwittayarak, Voraphat Trachoo, Jeeranan Manokawinchoke, Seung-Cheol Lee, Hiroshi Egusa, Jin Man Kim, Thanaphum Osathanon
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引用次数: 0

Abstract

Objectives: This study investigated the miRNA expression profile in Notch-activated human dental stem pulp stem cells (DPSCs) and validated the functions of miRNAs in modulating the odonto/osteogenic properties of DPSCs.

Methods: DPSCs were treated with indirect immobilized Jagged1. The miRNA expression profile was examined using NanoString analysis. Bioinformatic analysis was performed, and miRNA expression was validated. Odonto/osteogenic differentiation was examined using alkaline phosphatase staining, Alizarin Red S staining, as well as odonto/osteogenic-related gene and protein expression.

Results: Fourteen miRNAs were differentially expressed in Jagged1-treated DPSCs. Pathway analysis revealed that altered miRNAs were associated with TGF-β, Hippo, ErbB signalling pathways, FoxO and Ras signalling. Target prediction analysis demonstrated that 7604 genes were predicted to be targets for these altered miRNAs. Enrichment analysis revealed relationships to various DNA bindings. Among differentially expressed miRNA, miR-296-3p and miR-450b-5p were upregulated under Jagged1-treated conditions. Overexpression of miR-296-3p and miR-450b-5p enhanced mineralization and upregulation of odonto/osteogenic-related genes, whereas inhibition of these miRNAs revealed opposing results. The miR-296-3p and miR-450b-5p inhibitors attenuated the effects of Jagged1-induced mineralization in DPSCs.

Conclusions: Jagged-1 promotes mineralization in DPSCs that are partially regulated by miRNA. The novel understanding of these miRNAs could lead to innovative controlled mechanisms that can be applied to modulate biology-targeted dental materials.

Notch信号通过微RNA调节牙髓干细胞的矿化。
研究目的本研究调查了Notch激活的人牙髓干细胞(DPSCs)中miRNA的表达谱,并验证了miRNA在调节DPSCs牙髓/骨生成特性中的功能:方法:用间接固定的 Jagged1 处理 DPSCs。方法:用间接固定的 Jagged1 处理 DPSCs,使用 NanoString 分析法检测 miRNA 的表达谱。进行了生物信息学分析,并验证了 miRNA 的表达。利用碱性磷酸酶染色法、茜素红 S 染色法以及畸形/骨化相关基因和蛋白质的表达来检测畸形/骨化分化:结果:14个miRNA在经Jagged1处理的DPSCs中差异表达。通路分析显示,改变的 miRNA 与 TGF-β、Hippo、ErbB 信号通路、FoxO 和 Ras 信号有关。靶标预测分析表明,有 7604 个基因被预测为这些改变的 miRNAs 的靶标。富集分析显示了与各种 DNA 结合的关系。在差异表达的 miRNA 中,miR-296-3p 和 miR-450b-5p 在 Jagged1 处理条件下上调。miR-296-3p和miR-450b-5p的过表达促进了矿化和畸形/骨生成相关基因的上调,而抑制这些miRNA则会产生相反的结果。miR-296-3p和miR-450b-5p抑制剂减弱了Jagged1诱导的DPSCs矿化作用:结论:Jagged-1促进DPSCs矿化的作用部分受miRNA调控。对这些 miRNA 的新认识可能会带来创新的控制机制,可用于调节生物靶向牙科材料。
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来源期刊
Oral diseases
Oral diseases 医学-牙科与口腔外科
CiteScore
7.60
自引率
5.30%
发文量
325
审稿时长
4-8 weeks
期刊介绍: Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.
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