长链非编码RNA MIR4435-2HG参与人牙髓干细胞成骨分化和炎症

IF 3.2 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

International dental journal Pub Date : 2025-06-25 DOI:10.1016/j.identj.2025.100866

Feijun Wu , Zhisheng Jiang

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引用次数: 0

摘要

牙髓炎是一种常见的口腔疾病，有必要对其发病机制和治疗靶点进行研究。本研究旨在阐明长链非编码RNA MIR4435-2宿主基因（MIR4435-2HG）在体外牙髓细胞成骨分化和炎症反应中的功能，为牙髓炎的机制和潜在的治疗策略提供新的见解。方法采用实时荧光定量PCR法检测髓样中MIR4435-2HG的表达。利用人牙髓干细胞（hDPSCs）研究MIR4435-2HG对成骨分化的影响。用脂多糖（LPS）处理hdpsc诱导炎症反应。采用细胞计数试剂盒-8和细胞凋亡法分别检测hDPSCs的活力和凋亡。通过双荧光素酶报告基因测定证实了MIR4435-2HG和miR-296-5p之间的靶向关系。结果smir4435 - 2hg在炎症牙髓组织中表达上调，在区分健康牙髓和炎症牙髓方面表现出良好的作用。在成骨诱导的hDPSCs中，MIR4435-2HG抑制碱性磷酸酶活性和成骨标志物（牙本质基质蛋白-1和牙本质唾液磷酸化蛋白）的表达。在lps刺激的hDPSCs中，MIR4435-2HG的敲低降低了炎症介质（TNF-α、IL-1β和IL-6）的mRNA水平，促进了细胞增殖，抑制了细胞凋亡。miR-296-5p被MIR4435-2HG负向调节，miR-296-5p的下调抵消了MIR4435-2HG敲低对炎症和细胞表型的影响。结论MIR4435-2HG抑制成骨分化，同时通过miR-296-5p调控促进脂多糖引发的hdpsc炎症。本研究探讨了MIR4435-2HG如何调节hDPSCs的成骨分化并调节lps诱导的炎症反应。研究结果揭示了其可能参与牙髓炎的发病机制，并提示其在牙组织修复方面的治疗潜力。

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Long Noncoding RNA MIR4435-2HG is Involved in Osteogenic Differentiation and Inflammation in Human Dental Pulp Stem Cells

Introduction and aims

Pulpitis is a common oral pathology, necessitating an investigation into its pathogenesis and therapeutic targets. The aim of this study was to elucidate the function of long noncoding RNA MIR4435-2 host gene (MIR4435-2HG) in osteogenic differentiation and inflammatory response of dental pulp cells in vitro, offering insights into pulpitis mechanisms and potential treatment strategies.

Methods

The expression of MIR4435-2HG was quantified by real-time quantitative PCR in pulp samples. Human dental pulp stem cells (hDPSCs) were utilized to investigate the impact of MIR4435-2HG on osteogenic differentiation. Inflammatory responses were induced by treating hDPSCs with lipopolysaccharide (LPS). The viability and apoptosis of hDPSCs were determined using Cell Counting Kit-8 and Apoptosis assays, respectively. The targeting relationship between MIR4435-2HG and miR-296-5p was substantiated using Dual-Luciferase reporter gene assay.

Results

MIR4435-2HG was upregulated in the inflamed pulp tissues and exhibited favourable efficacy in differentiating between healthy and inflamed pulp. In osteogenesis-induced hDPSCs, MIR4435-2HG suppressed alkaline phosphatase activity and the expression of osteogenic markers (dentin matrix protein-1 and dentin salivary phosphoprotein). In LPS-stimulated hDPSCs, knockdown of MIR4435-2HG decreased the mRNA levels of inflammatory mediators (TNF-α, IL-1β, and IL-6), promoted cell proliferation, and repressed apoptosis. miR-296-5p was negatively modulated by MIR4435-2HG, and downregulation of miR-296-5p counteracted the effects of MIR4435-2HG knockdown on inflammation and cellular phenotype.

Conclusion

The present investigation indicates that MIR4435-2HG suppresses osteogenic differentiation while facilitating LPS-triggered inflammation in hDPSCs through miR-296-5p modulation.

Clinical relevance

This study investigated how MIR4435-2HG regulates osteogenic differentiation in hDPSCs and modulates LPS-induced inflammatory reactions. The findings shed light on its possible involvement in pulpitis pathogenesis and suggest its therapeutic potential for dental tissue repair.

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来源期刊

International dental journal 医学-牙科与口腔外科

CiteScore

4.80

自引率

6.10%

发文量

159

审稿时长

63 days

期刊介绍： The International Dental Journal features peer-reviewed, scientific articles relevant to international oral health issues, as well as practical, informative articles aimed at clinicians.