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Effect of Tension on Human Periodontal Ligament Cells: Systematic Review and Network Analysis

ABSTRACT: Orthodontic tooth movement is based on the remodeling of tooth-surrounding tissues in response to mechanical stimuli. During this process, human periodontal ligament cells (hPDLCs) play a central role in mechanosensing and mechanotransduction. Various in vitro models have been introduced to investigate the effect of tension on hPDLCs. They provide a valuable body of knowledge on how tension influences relevant genes, proteins, and metabolites. However, no systematic review summarizing these findings has been conducted so far. Aim of this systematic review was to identify all related in vitro studies reporting tension application on hPDLCs and summarize their findings regarding force parameters, including magnitude, frequency and duration. Expression data of genes, proteins, and metabolites was extracted and summarized. Studies’ risk of bias was assessed using tailored risk of bias tools. Signaling pathways were identified by protein-protein interaction (PPI) networks using STRING and GeneAnalytics. According to our results, Flexcell Strain Unit® and other silicone-plate or elastic membrane-based apparatuses were mainly adopted. Frequencies of 0.1 and 0.5 Hz were predominantly applied for dynamic equibiaxial and uniaxial tension, respectively. Magnitudes of 10 and 12% were mostly employed for dynamic tension and 2.5% for static tension. The 10 most commonly investigated genes, proteins and metabolites identified, were mainly involved in osteogenesis, osteoclastogenesis or inflammation. Gene-set enrichment analysis and PPI networks gave deeper insight into the involved signaling pathways. This review represents a brief summary of the massive body of knowledge in this field, and will also provide suggestions for future researches on this topic.

SUBMITTER: Sun C

PROVIDER: S-EPMC8429507 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe periodontal ligament is essential for homeostasis of periodontal tissue. A hypoxic milieu of the periodontal tissue is generated under periodontitis or during orthodontic treatment, which affects the periodontal and bone remodelling process. Here, we provide a comprehensive proteomic characterization of periodontal ligament cells under hypoxic conditions, aiming to reveal previously unappreciated biological changes and to help advance hypoxia-based therapeutic strategies for periodontal diseases.MethodsHuman periodontal ligament cells (hPDLCs) were characterized using immunohistochemistry (IHC) and flow cytometry (FACS). Successful hypoxia treatment of hPDLCs with 1% O2 was confirmed by qRT-PCR. Proliferation was evaluated using an MTT assay. The proteomic expression profile under hypoxia was studied with the isobaric tags for relative and absolute quantification (iTRAQ) approach followed by protein identification and bioinformatic analysis, and western blot verification was performed.ResultsThe hPDLCs were positive for vimentin, CD73 and CD105 and negative for keratin, CD34 and CD45. After hypoxia treatment, the mRNA expression of hypoxia-inducible factor 1a (HIF1a) was upregulated. The proliferation rate was elevated during the first 6 h but decreased from 6 h to 72 h. A total of 220 differentially expressed proteins were quantified in hPDLCs under hypoxia (1% O2, 24 h), including 153 upregulated and 67 downregulated proteins, five of which were verified by western blot analysis. The Gene Ontology enriched terms included the energy metabolic process, membrane-bound organelle and vesicle, and protein binding terms. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated several involved pathways, including glycolysis/gluconeogenesis, biosynthesis of amino acids, the HIF-1 signalling pathway, and focal adhesion. A protein-protein interaction (PPI) network demonstrated the dominant role of autophagy over apoptosis under hypoxia.ConclusionThe proteomic profile of hPDLCs under hypoxia was mainly related to energy metabolism, autophagy, and responses to stimuli such as adhesion and inflammation. Previously unrecognized proteins including solute carrier family proteins, heat shock proteins, ubiquitination-related enzymes, collagen and S100 family proteins are involved in adaptive response to hypoxia in hPDLCs and are thus of great research interest in future work.

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Effect of Tension on Human Periodontal Ligament Cells: Systematic Review and Network Analysis

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