Department of Stomatology, First Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
Department of Orthodontics, Yantai Stomatological Hospital Affiliated to Binzhou Medical College, Yantai, China.
Eur J Oral Sci. 2022 Oct;130(5):e12891. doi: 10.1111/eos.12891. Epub 2022 Aug 15.
The molecular mechanisms underlying osteogenic differentiation of periodontal ligament stem cells (PDLSCs) under mechanical tension remain unclear. This study aimed to identify a potential long non-coding ribonucleic acids (lncRNAs)/circular RNAs (circRNAs)-microRNAs (miRNAs)-messenger RNAs (mRNAs) network in mechanical tension-induced osteogenic differentiation of PDLSCs. PDLSCs were isolated from the healthy human periodontal ligament, identified, cultured, and exposed to tensile force. The expression of osteogenic markers was examined, and whole transcriptome sequencing was performed to identify the expression patterns of lncRNA, circRNA, miRNAs, and mRNAs. Enrichment analyses were also performed. Candidate targets of differentially expressed non-coding RNAs (ncRNAs) were predicted, and potential competitive endogenous RNA (ceRNA) networks were constructed by Cytoscape. We found that the osteogenic differentiation of PDLSCs was significantly enhanced under dynamic tension (magnitude: 12%, frequency: 0.7 Hz). Overall, 344 lncRNAs, 57 miRNAs, 41 circRNAs, and 70 mRNAs were differentially expressed in the tension group and the control group. Functional enrichment analysis showed that differentially expressed mRNAs were mainly enriched in osteogenesis-related and mechanical stress-related biological processes and signal transduction pathways (e.g., tumor necrosis factor [TNF] and Hippo signaling pathways). The lncRNA/circRNA-miRNA-mRNA networks were depicted, and potential key ceRNA networks were identified. Our findings may help to further explore the underlying regulatory mechanism of osteogenic differentiation of PDLSCs under mechanical tensile stress.
牙周膜干细胞（PDLSCs）在机械张力下成骨分化的分子机制尚不清楚。本研究旨在鉴定机械张力诱导的 PDLSCs 成骨分化过程中潜在的长链非编码 RNA（lncRNA）/环状 RNA（circRNA）-微小 RNA（miRNA）-信使 RNA（mRNA）网络。从健康人牙周膜中分离、鉴定、培养 PDLSCs，并施加张力。检测成骨标志物的表达，并进行全转录组测序以鉴定 lncRNA、circRNA、miRNA 和 mRNA 的表达模式。还进行了富集分析。预测差异表达非编码 RNA（ncRNA）的候选靶标，并通过 Cytoscape 构建潜在的竞争性内源性 RNA（ceRNA）网络。我们发现动态张力（幅度：12%，频率：0.7 Hz）显著增强了 PDLSCs 的成骨分化。总体而言，张力组和对照组中差异表达的 lncRNA 有 344 个，miRNA 有 57 个，circRNA 有 41 个，mRNA 有 70 个。功能富集分析表明，差异表达的 mRNAs 主要富集在与成骨和机械应激相关的生物学过程和信号转导途径（如肿瘤坏死因子[TNF]和 Hippo 信号通路）中。描绘了 lncRNA/circRNA-miRNA-mRNA 网络，并鉴定了潜在的关键 ceRNA 网络。我们的研究结果可能有助于进一步探索机械拉伸应力下 PDLSCs 成骨分化的潜在调控机制。
