炎症环境下LncRNA H19通过NRF-2/HO-1信号通路调控牙周膜干细胞骨向诱导分化的机制研究

doi:10.19439/j.sjos.2025.06.003

上海口腔医学 ›› 2025, Vol. 34 ›› Issue (6): 577-582.doi: 10.19439/j.sjos.2025.06.003

炎症环境下LncRNA H19通过NRF-2/HO-1信号通路调控牙周膜干细胞骨向诱导分化的机制研究

钱毅^1,2, 许晓波^3,4, 伍燕⁵, 宫文婷^1,2, 卢军^1,2, 刘守红^1,2

1.安徽医科大学第一附属医院口腔科, 安徽合肥 230012;
2.安徽省公共卫生临床中心, 安徽合肥 230012;
3.合肥市口腔医院修复科, 安徽合肥 230061;
4.安徽医科大学合肥口腔临床学院, 安徽合肥 230061;
5.贵阳市口腔医院牙周病科, 贵州贵阳 550000

收稿日期:2025-04-08 修回日期:2025-05-22 发布日期:2025-12-30
通讯作者: 伍燕,E-mail: 330796865@qq.com
作者简介:钱毅(1978-),男,硕士,主任医师,E-mail: yfyb12820022@fy.ahmu.edu.cn
基金资助:
安徽医科大学校研基金项目（临床科学基金）（2021xkj180）; 贵阳市卫生健康局高层次创新型青年卫生人才培养计划项目（2021筑卫健科技合同字第40号）; 贵州省卫生健康委科学技术基金项目（gzwkj-2023-441）

Mechanism of LncRNA H19 regulation of bone-directed induced differentiation of periodontal stem cells through NRF-2/HO-1 signaling pathway in inflammatory microenvironment

Qian Yi^1,2, Xu Xiaobo^3,4, Wu Yan⁵, Gong Wenting^1,2, Lu Jun^1,2, Liu Shouhong^1,2

1. Department of Stomatology, First Affiliated Hospital of Anhui Medical University. Hefei 230012, Anhui Province;
2. Anhui Public Health Clinical Center. Hefei 230012, Anhui Province;
3. Department of Prosthodontics, Anhui Medical University Dental Hospital, Hefei Stomatological Hospital. Hefei 230061, Anhui Province;
4. Hefei Clinical College of Stomatology, Anhui Medical University. Hefei 230061, Anhui Province;
5. Department of Periodontology, Guiyang Hospital of Stomatology. Guiyang 550000, Guizhou Province, China

Received:2025-04-08 Revised:2025-05-22 Published:2025-12-30

摘要/Abstract

摘要： 目的:研究炎症环境下长链非编码LncRNA H19对牙周膜干细胞骨向分化的影响及机制。方法:对牙周膜干细胞进行成骨、成脂诱导,使用茜素红染色和油红O染色观察牙周膜干细胞骨向分化和脂向分化情况,检测牙周膜干细胞骨向分化前后成骨相关基因RUNX-2、ALP和BSP的表达变化,以及LncRNA H19的表达量变化。将细胞置于炎症环境中,检测成骨相关基因RUNX-2、ALP、BSP的表达,以及LncRNA H19和NRF-2/HO-1表达。使用慢病毒转染细胞上调LncRNA H19后,检测成骨相关基因RUNX-2、ALP和BSP以及NRF-2/HO-1的表达。结果:牙周膜干细胞具有干细胞特性,可被诱导进行骨向和脂向分化。牙周膜干细胞在骨向分化过程中,成骨相关基因RUNX-2、ALP、BSP的表达以及LncRNA H19的表达均升高;炎症状态下牙周膜干细胞成骨相关基因RUNX-2、ALP、BSP表达下调,LncRNA H19、NRF-2/HO-1表达量下降。当细胞中LncRNA H19上调后,NRF-2/HO-1、RUNX-2、ALP、BSP表达量升高。结论:炎症微环境可能通过降低LncRNA H19的表达,抑制NRF-2/HO-1信号通路,从而导致牙周膜干细胞骨向分化能力降低。

关键词: LncRNA H19, NRF-2/HO-1信号通路, 牙周膜干细胞, 骨向分化

Abstract: PURPOSE: To investigate the effect and underlying mechanism of long non-coding RNA H19 on the osteogenic differentiation of periodontal ligament stem cells(PDLSCs) under inflammatory conditions. METHODS: PDLSCs were subjected to osteogenic and adipogenic induction. Alizarin Red staining and Oil Red O staining were used to observe osteogenic and adipogenic differentiation, respectively. The expression levels of osteogenesis-related genes RUNX-2, ALP, and BSP, as well as LncRNA H19, were measured before and after osteogenic induction. Cells were also cultured in an inflammatory environment to assess the expression of RUNX-2, ALP, BSP, LncRNA H19 and NRF-2/HO-1. Furthermore, LncRNA H19 was upregulated via lentiviral transfection, and subsequent changes in the expression of osteogenic genes (RUNX-2, ALP, BSP) and NRF-2/HO-1 were analyzed. RESULTS: PDLSCs had stem cell properties and could be induced to undergo osteogenic and adipogenic differentiation. During osteogenic differentiation, the expression of osteogenic genes RUNX-2, ALP, BSP and LncRNA H19 increased. Under inflammatory conditions, the expression of RUNX-2, ALP, BSP and LncRNA H19 was downregulated, along with a decrease in NRF-2/HO-1 expression. Upregulation of LncRNA H19 resulted in increased expression of NRF-2/HO-1 as well as osteogenic genes RUNX-2, ALP and BSP. CONCLUSIONS: The inflammatory microenvironment may suppress osteogenic differentiation of PDLSCs by reducing LncRNA H19 expression, which in turn inhibits the NRF-2/HO-1 signaling pathway.

Key words: LncRNAH19, NRF-2/HO-1 signaling pathway, Periodontal stem cells, Bone-oriented differentiation

中图分类号:

R781.4
Q254

钱毅, 许晓波, 伍燕, 宫文婷, 卢军, 刘守红. 炎症环境下LncRNA H19通过NRF-2/HO-1信号通路调控牙周膜干细胞骨向诱导分化的机制研究[J]. 上海口腔医学, 2025, 34(6): 577-582.

Qian Yi, Xu Xiaobo, Wu Yan, Gong Wenting, Lu Jun, Liu Shouhong. Mechanism of LncRNA H19 regulation of bone-directed induced differentiation of periodontal stem cells through NRF-2/HO-1 signaling pathway in inflammatory microenvironment[J]. Shanghai Journal of Stomatology, 2025, 34(6): 577-582.

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炎症环境下LncRNA H19通过NRF-2/HO-1信号通路调控牙周膜干细胞骨向诱导分化的机制研究

Mechanism of LncRNA H19 regulation of bone-directed induced differentiation of periodontal stem cells through NRF-2/HO-1 signaling pathway in inflammatory microenvironment

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