柚皮素通过与 AKT 结合调节 NO-cGMP-PKG 信号通路,从而增强 hPDLSCs 的成骨分化。

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
International journal of molecular medicine Pub Date : 2024-08-01 Epub Date: 2024-06-28 DOI:10.3892/ijmm.2024.5391
Shenghong Li, Zhenqiang Xiong, Yuxin Lan, Qian Zheng, Li Zhang, Xiaomei Xu
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引用次数: 0

摘要

柚皮苷(NAR)是一种重要的黄烷酮类化合物,因其具有促进人牙周韧带干细胞(hPDLSCs)成骨分化的能力而得到认可。本研究旨在探索 NAR 如何促进 hPDLSCs 的成骨分化,并评估其修复牙槽骨缺损的功效。为此,通过mRNA测序和网络药理学分析建立了NAR作用的蛋白-蛋白相互作用网络。基因和蛋白质表达水平通过反转录定量和免疫印迹法进行评估。茜素红和碱性磷酸酶染色也用于观察 hPDLSCs 的成骨能力,免疫荧光用于检测 NAR 分子探针和 AKT 在细胞中的共定位。通过微型计算机断层扫描(micro-CT)、Masson 染色和免疫荧光评估了下颌骨缺损的修复情况。此外,还利用计算机模拟对接软件确定了 NAR 与目标蛋白 AKT 的结合亲和力。结果表明,激活一氧化氮(NO)-单磷酸环鸟苷(cGMP)-蛋白激酶G(PKG)信号通路可促进hPDLSCs的成骨分化。抑制AKT、内皮一氧化氮合酶和可溶性鸟苷酸环化酶可单独削弱NAR促进hPDLSCs成骨分化的能力。显微 CT 和 Masson 染色显示,NAR 灌胃组在缺损部位有更多新骨形成。免疫荧光检测证实,NAR灌胃组中Runt相关转录因子2和骨素的表达上调。总之,本研究的结果表明,NAR通过与AKT结合激活NO-cGMP-PKG信号通路,促进了hPDLSCs的成骨分化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Naringenin modulates the NO‑cGMP‑PKG signaling pathway by binding to AKT to enhance osteogenic differentiation in hPDLSCs.

Naringenin (NAR) is a prominent flavanone that has been recognized for its capacity to promote the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). The present study aimed to explore how NAR promotes the osteogenic differentiation of hPDLSCs and to assess its efficacy in repairing alveolar bone defects. For this purpose, a protein‑protein interaction network of NAR action was established by mRNA sequencing and network pharmacological analysis. Gene and protein expression levels were evaluated by reverse transcription‑quantitative and western blotting. Alizarin red and alkaline phosphatase staining were also employed to observe the osteogenic capacity of hPDLSCs, and immunofluorescence was used to examine the co‑localization of NAR molecular probes and AKT in cells. The repair of mandibular defects was assessed by micro‑computed tomography (micro‑CT), Masson staining and immunofluorescence. Additionally, computer simulation docking software was utilized to determine the binding affinity of NAR to the target protein, AKT. The results demonstrated that activation of the nitric oxide (NO)‑cyclic guanosine monophosphate (cGMP)‑protein kinase G (PKG) signaling pathway could promote the osteogenic differentiation of hPDLSCs. Inhibition of AKT, endothelial nitric oxide synthase and soluble guanylate cyclase individually attenuated the ability of NAR to promote the osteogenic differentiation of hPDLSCs. Micro‑CT and Masson staining revealed that the NAR gavage group exhibited more new bone formation at the defect site. Immunofluorescence assays confirmed the upregulated expression of Runt‑related transcription factor 2 and osteopontin in the NAR gavage group. In conclusion, the results of the present study suggested that NAR promotes the osteogenic differentiation of hPDLSCs by activating the NO‑cGMP‑PKG signaling pathway through its binding to AKT.

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来源期刊
International journal of molecular medicine
International journal of molecular medicine 医学-医学:研究与实验
CiteScore
12.30
自引率
0.00%
发文量
124
审稿时长
3 months
期刊介绍: The main aim of Spandidos Publications is to facilitate scientific communication in a clear, concise and objective manner, while striving to provide prompt publication of original works of high quality. The journals largely concentrate on molecular and experimental medicine, oncology, clinical and experimental cancer treatment and biomedical research. All journals published by Spandidos Publications Ltd. maintain the highest standards of quality, and the members of their Editorial Boards are world-renowned scientists.
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