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

Jia Liu,Chunrong Li,Shuangyun Liu,Zuolin Jin,Yan Zhao,Cuixia Li,Ni Qiu,Qiannan Niu,Libo Yan,Pei Miao,Qiang Li,Yohei Hayashi

doi:10.1155/2021/6655526

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.

Highlights

Periodontitis is a chronic inflammatory disease that causes irreversible periodontal attachment damage [1]
We identified thousands of DElncRNAs and DEmRNAs in HPDLSCs and PPDLSCs after static mechanical strain (SMS) application, and various Long noncoding RNAs (lncRNAs) and mRNAs were found to be solely expressed in strained HPDLSCs or PPDLSCs, indicating that different mechanisms may be involved in the mechanotransductive responses of Periodontal ligament stem cells (PDLSCs) derived from different contexts
Differentially expressed lncRNA profiles between HPDLSCs and PDLSCs under mechanical exposure were first identified in this study, and many were expressed

Summary

Introduction

Periodontitis is a chronic inflammatory disease that causes irreversible periodontal attachment damage [1]. Our previous studies revealed that PDLSCs obtained from periodontal tissues of periodontitis patients (PPDLSCs) are characterized by impaired function that leads to aberrant proliferative and osteogenic properties [5, 6]. Mechanical stimuli are another critical factor affecting tissue homeostasis and function. PPDLSCs display a sensitive pattern of both decreased proliferation and osteogenesis and an active inflammatory response to SMS at 12% elongation, while PDLSCs obtained from healthy periodontal tissues (HPDLSCs) exhibit a notable promotion of multidirectional capacities [6]

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