Li Zhi-Bang, Yang Hui-Qi, Li Kun, Yin Yuan, Feng Su-Su, Ge Shao-Hua, Yu Yang
Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China.
State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, School of Stomatology, Fourth Military Medical University, Xi'an, China.
Front Genet. 2022 Feb 8;13:797055. doi: 10.3389/fgene.2022.797055. eCollection 2022.
Short-term hypoxia pretreatment significantly enhances periodontal ligament stem cell (PDLSC)-based periodontal tissue regeneration by improving various cellular biological functions, but the underlying mechanisms remain unclear. In this study, based on RNA sequencing (RNA-seq), we comprehensively analyzed the possible regulatory mechanisms of the short-term hypoxic effects on the biological functions of healthy and inflammatory PDLSCs. A total of 134 and 164 differentially expressed genes (DEGs) were identified under healthy and inflammatory conditions, respectively. Functional enrichment analyses indicated that DEGs under both conditions share certain biological processes and pathways, including metabolic processes, developmental processes, reproductive processes, localization, immune system processes and the HIF-1 signaling pathway. The DEGs identified under inflammatory conditions were more significantly enriched in cell cycle-related processes and immune-related pathways, while DEGs identified under healthy condition were more significantly enriched in the TGF-β signaling pathway. A protein-protein interaction network analysis of the 59 DEGs in both conditions was performed, and 15 hub genes were identified. These hub genes were mainly involved in glycolysis, the cellular response to hypoxia, cell differentiation, and immune system processes. In addition, we found that hypoxia induced significant differential expression of genes associated with proliferation, differentiation, migration, apoptosis and immunoregulation under both healthy and inflammatory conditions. This study provides comprehensive insights into the effects of short-term hypoxia on the biological functions of PDLSCs and suggests a potentially feasible strategy for improving the clinical effectiveness of cell-based periodontal tissue engineering.
短期缺氧预处理通过改善多种细胞生物学功能，显著增强了基于牙周膜干细胞（PDLSC）的牙周组织再生能力，但其潜在机制仍不清楚。在本研究中，基于RNA测序（RNA-seq），我们全面分析了短期缺氧对健康和炎症状态下PDLSCs生物学功能的可能调控机制。在健康和炎症条件下，分别鉴定出134个和164个差异表达基因（DEG）。功能富集分析表明，两种条件下的DEG共享某些生物学过程和途径，包括代谢过程、发育过程、生殖过程、定位、免疫系统过程和HIF-1信号通路。在炎症条件下鉴定出的DEG在细胞周期相关过程和免疫相关途径中更显著富集，而在健康条件下鉴定出的DEG在TGF-β信号通路中更显著富集。对两种条件下的59个DEG进行了蛋白质-蛋白质相互作用网络分析，鉴定出15个枢纽基因。这些枢纽基因主要参与糖酵解、细胞对缺氧的反应、细胞分化和免疫系统过程。此外，我们发现缺氧在健康和炎症条件下均诱导了与增殖、分化、迁移、凋亡和免疫调节相关基因的显著差异表达。本研究全面深入地了解了短期缺氧对PDLSCs生物学功能的影响，并提出了一种潜在可行的策略来提高基于细胞的牙周组织工程的临床效果。
