Nile Mustafa, Folwaczny Matthias, Wichelhaus Andrea, Baumert Uwe, Janjic Rankovic Mila
Department of Orthodontics and Dentofacial Orthopedics, LMU University Hospital, LMU Munich, Munich, Germany.
Department of Conservative Dentistry and Periodontology, LMU University Hospital, LMU Munich, Munich, Germany.
Front Bioeng Biotechnol. 2023 Sep 18;11:1256825. doi: 10.3389/fbioe.2023.1256825. eCollection 2023.
This study aimed to identify and analyze studies investigating the biological effect of fluid-flow shear stress (FSS) on cells found in the periodontal ligament and bone tissue. We followed the PRISMA guideline for systematic reviews. A PubMed search strategy was developed, studies were selected according to predefined eligibility criteria, and the risk of bias was assessed. Relevant data related to cell source, applied FSS, and locus-specific expression were extracted. Based on this evidence synthesis and, as an original part of this work, analysis of differential gene expression using over-representation and network-analysis was performed. Five relevant publicly available gene expression datasets were analyzed using gene set enrichment analysis (GSEA). A total of 6,974 articles were identified. Titles and abstracts were screened, and 218 articles were selected for full-text assessment. Finally, 120 articles were included in this study. Sample size determination and statistical analysis related to methodological quality and the ethical statement item in reporting quality were most frequently identified as high risk of bias. The analyzed studies mostly used custom-made fluid-flow apparatuses (61.7%). FSS was most frequently applied for 0.5 h, 1 h, or 2 h, whereas FSS magnitudes ranged from 6 to 20 dyn/cm depending on cell type and flow profile. Fluid-flow frequencies of 1 Hz in human cells and 1 and 5 Hz in mouse cells were mostly applied. FSS upregulated genes/metabolites responsible for tissue formation (AKT1, alkaline phosphatase, BGLAP, BMP2, Ca, COL1A1, CTNNB1, GJA1, MAPK1/MAPK3, PDPN, RUNX2, SPP1, TNFRSF11B, VEGFA, WNT3A) and inflammation (nitric oxide, PGE-2, PGI-2, PTGS1, PTGS2). Protein-protein interaction networks were constructed and analyzed using over-representation analysis and GSEA to identify shared signaling pathways. To our knowledge, this is the first review giving a comprehensive overview and discussion of methodological technical details regarding fluid flow application in 2D cell culture experimental conditions. Therefore, it is not only providing valuable information about cellular molecular events and their quantitative and qualitative analysis, but also confirming the reproducibility of previously published results.
本研究旨在识别和分析有关研究流体流动切应力（FSS）对牙周韧带和骨组织中细胞生物学效应的研究。我们遵循PRISMA系统评价指南。制定了PubMed检索策略，根据预先确定的纳入标准选择研究，并评估偏倚风险。提取了与细胞来源、施加的FSS以及位点特异性表达相关的相关数据。基于这一证据综合，并作为本工作的原创部分，使用过表达和网络分析对差异基因表达进行了分析。使用基因集富集分析（GSEA）对五个相关的公开可用基因表达数据集进行了分析。共识别出6974篇文章。筛选了标题和摘要，选择了218篇文章进行全文评估。最后，本研究纳入了120篇文章。样本量确定以及与方法学质量和报告质量中的伦理声明项相关的统计分析最常被确定为高偏倚风险。分析的研究大多使用定制的流体流动装置（61.7%）。FSS最常施加0.5小时、1小时或2小时，而FSS大小根据细胞类型和流动剖面在6至20达因/平方厘米范围内。在人类细胞中大多施加1赫兹的流体流动频率，在小鼠细胞中大多施加1赫兹和5赫兹的流体流动频率。FSS上调了负责组织形成（AKT1、碱性磷酸酶、骨钙素、骨形态发生蛋白2、钙、胶原蛋白1A1、β-连环蛋白、缝隙连接蛋白43、丝裂原活化蛋白激酶1/丝裂原活化蛋白激酶3、Podoplanin、RUNX2、骨桥蛋白、肿瘤坏死因子受体超家族成员11B、血管内皮生长因子A、WNT3A）和炎症（一氧化氮、前列腺素E-2、前列环素I-2、前列腺素内过氧化物合酶1、前列腺素内过氧化物合酶2）的基因/代谢物。构建并使用过表达分析和GSEA分析蛋白质-蛋白质相互作用网络，以识别共享的信号通路。据我们所知，这是第一篇全面概述和讨论二维细胞培养实验条件下流体流动应用方法技术细节的综述。因此，它不仅提供了有关细胞分子事件及其定量和定性分析的有价值信息，还证实了先前发表结果的可重复性。
