Long Noncoding RNA Expression Profiles of Periodontal Ligament Stem Cells from the Periodontitis Microenvironment in Response to Static Mechanical Strain

Abstract

During the period of orthodontic tooth movement, periodontal ligament stem cells (PDLSCs) play an important role in transducing mechanical stimulation and tissue remodeling. However, our previous studies verified that the periodontitis microenvironment causes damage to the biological functions of PDLSCs and abnormal mechanical sensitivity. Long noncoding RNAs (lncRNAs) participate in the inflammatory pathogenesis and development of many diseases. Whether lncRNAs are abnormally expressed in PDLSCs obtained from periodontal tissues of periodontitis patients (PPDLSCs) and whether putative lncRNAs participate in the mechanotransductive process in PDLSCs remain poorly understood. First, we subjected PDLSCs obtained from healthy periodontal tissues (HPDLSCs) and PPDLSCs to static mechanical strain (SMS) with 12% elongation at 0.1 Hz frequency using an FX-4000T system and screened overall lncRNA profiles in both cell types by microarray. Among lncRNAs with a fold change FC > 20.0 , 27 lncRNAs were upregulated in strained HPDLSCs, and 16 lncRNAs (9 upregulated and 7 downregulated) were detected in strained PPDLSCs. For mRNAs with FC > 20.0 , we detected 25 upregulated mRNAs and one downregulated mRNA in strained HPDLSCs and 7 upregulated and 5 downregulated mRNAs in strained PPDLSCs. Further enrichment analysis showed that, unlike HPDLSCs with annotations principally involving transduction-associated signaling pathways, dysregulated mRNAs in PPDLSCs are mainly responsible for pathological conditions. Moreover, coexpressed lncRNA-mRNA networks confirmed the pathological state and exacerbated inflammatory conditions in strained PPDLSCs. Taken together, when compared with strained HPDLSCs, various lncRNAs and mRNAs were dysregulated in PPDLSCs under mechanical forces, implicating the response of lncRNAs in PPDLSCs to mechanical stress. Moreover, we provide potential lncRNA targets, which may contribute to future intervention strategies for orthodontic treatment in periodontitis patients.

The Expression and Regulatory Roles of Long Non-Coding RNAs in Periodontal Ligament Cells: A Systematic Review

“…In total, 13 of the 50 studies broadly explored the expression profiling of PDL cells using microarray or RNA sequencing (RNA-seq) ( Table 1 ). These studies investigated the lncRNA expression profiles of PDL cells subjected to osteogenic induction [ 28 , 29 , 30 , 35 , 36 ] and mechanical stress [ 37 , 38 , 39 , 40 , 41 ]; some compared PDL cells’ expression profiles with those of other cell types, including bone marrow stem cells (BMSCs) [ 27 ], gingival mesenchymal stem cells (GMSCs) [ 42 ], and dental follicle cells (DFCs) [ 43 ].…”

“…In the 13 studies that explored lncRNA expression profiles in PDL cells, 6 used microarray analysis and 7 used RNA-seq methods [ 27 , 28 , 29 , 30 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. Recent developments in RNA-seq techniques offer enormous potential for transcriptome characterization as they are reliable tools for elucidating genetic and metabolic pathways involved in biological processes.…”

“…Moreover, differences in library preparation, sequencing techniques, and methods of analysis may also have led to the variations in the results. Five of the thirteen studies explored the lncRNA profile of PDL cells subjected to mechanical stress [ 37 , 38 , 39 , 40 , 41 ]. Three of these studies applied tensile force on cells (10% or 12% equibiaxial strain) [ 37 , 39 , 40 ] and one applied compressive force on cells (2 g/cm 2 ) for 12 h [ 38 ].…”

“…Five of the thirteen studies explored the lncRNA profile of PDL cells subjected to mechanical stress [ 37 , 38 , 39 , 40 , 41 ]. Three of these studies applied tensile force on cells (10% or 12% equibiaxial strain) [ 37 , 39 , 40 ] and one applied compressive force on cells (2 g/cm 2 ) for 12 h [ 38 ]. After microarray or RNA-seq, most studies performed only PCR to validate the expression of several genes.…”

Long Noncoding RNA and mRNA m6A Modification Analyses of Periodontal Ligament Stem Cells from the Periodontitis Microenvironment Exposed to Static Mechanical Strain

“…Long noncoding RNAs (lncRNAs), consisting of 200 or more nucleotides, regulate many biological and pathological processes and play roles in periodontitis [ 13 ]. Studies have reported amounts of lncRNAs that are differentially expressed between hPDLSCs and pPDLSCs exposed to SMS [ 14 ], and some of these lncRNAs affect the osteogenic differentiation capacity of PDLSCs [ 15 , 16 ]. For example, lncRNA-XIST promotes the osteogenesis of PDLSCs and is expressed at lower levels in strain-exposed pPDLSCs than in strain-exposed hPDLSCs [ 14 ].…”