LncRNA00638 促进牙周炎患者牙周膜干细胞在静态机械应变下的成骨分化。
LncRNA00638 promotes the osteogenic differentiation of periodontal mesenchymal stem cells from periodontitis patients under static mechanical strain.
机构信息
State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, China.
State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, China.
出版信息
Stem Cell Res Ther. 2023 Jul 11;14(1):177. doi: 10.1186/s13287-023-03404-6.
BACKGROUND
The osteogenic differentiation capacity of periodontal mesenchymal stem cells (PDLSCs) can be influenced by different levels of static mechanical strain (SMS) in an inflammatory microenvironment. Long non-coding RNAs (lncRNAs) are involved in various physiological processes. However, the mechanisms by which lncRNAs regulate the osteogenic differentiation of PDLSCs remain unclear.
METHODS
We investigated the responses of PDLSCs obtained from periodontitis patients and healthy people to 8% and 12%SMS. Gene microarray and bioinformatics analyses were implemented and identified lncRNA00638 as a target gene for the osteogenesis of PDLSCs from periodontitis patients under SMS. Competing endogenous RNA (ceRNA) network analysis was applied and predicted interactions among lncRNA00638, miRNA-424-5p, and fibroblast growth factor receptor 1 (FGFR1). Gene expression levels were regulated by lentiviral vectors. Cell Counting Kit-8 assays, alkaline phosphatase assays, and Alizarin Red S staining were used to examine the osteogenic potential. RT-qPCR and Western blot were performed to detect the expression levels of related genes and proteins.
RESULTS
We found that 8% and 12% SMS exerted distinct effects on HPDLSCs and PPDLSCs, with 12% SMS having the most significant effect. By microarray analysis, we detected differentially expressed lncRNAs/mRNAs between 12% SMS strained and static PPDLSCs, among which lncRNA00638 was detected as a positive target gene to promote the osteogenic differentiation of PPDLSCs under SMS loading. Mechanistically, lncRNA00638 may act as a ceRNA for miR-424-5p to compete with FGFR1. In this process, lncRNA00638 and miR-424-5p suppress each other and form a network to regulate FGFR1.
CONCLUSIONS
Our findings demonstrate that the lncRNA00638/miRNA-424-5p/FGFR1 regulatory network is actively involved in the regulation of PDLSC osteogenic differentiation from periodontitis patients under SMS loading, which may provide evidence for optimizing orthodontic treatments in patients with periodontitis.
背景
牙周膜干细胞（PDLSCs）的成骨分化能力会受到炎症微环境中不同水平静态机械应变（SMS）的影响。长链非编码 RNA（lncRNA）参与多种生理过程。然而，lncRNA 调节 PDLSC 成骨分化的机制尚不清楚。
方法
我们研究了来自牙周炎患者和健康人的 PDLSCs 对 8%和 12%SMS 的反应。进行基因微阵列和生物信息学分析，鉴定出 lncRNA00638 是 SMS 下牙周炎患者 PDLSCs 成骨的靶基因。应用竞争性内源性 RNA（ceRNA）网络分析预测 lncRNA00638、miRNA-424-5p 和成纤维细胞生长因子受体 1（FGFR1）之间的相互作用。通过慢病毒载体调节基因表达水平。使用细胞计数试剂盒-8 检测、碱性磷酸酶检测和茜素红 S 染色来检测成骨潜能。进行 RT-qPCR 和 Western blot 检测相关基因和蛋白的表达水平。
结果
我们发现 8%和 12%SMS 对 HPDLSCs 和 PPDLSCs 产生了不同的影响，其中 12%SMS 的影响最大。通过微阵列分析，我们在 12%SMS 应变和静态 PPDLSCs 之间检测到差异表达的 lncRNA/mRNA，其中 lncRNA00638 被检测为促进 SMS 加载下 PPDLSCs 成骨分化的阳性靶基因。在机制上，lncRNA00638 可能作为 miR-424-5p 的 ceRNA 与其竞争以调节 FGFR1。在这个过程中，lncRNA00638 和 miR-424-5p 相互抑制并形成网络以调节 FGFR1。
结论
我们的研究结果表明，lncRNA00638/miRNA-424-5p/FGFR1 调控网络积极参与调节 SMS 加载下牙周炎患者 PDLSC 的成骨分化，这可能为优化牙周炎患者的正畸治疗提供依据。
Zotero 插件