Review
Non-coding RNAs in endodontic disease

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Abstract

The immunocompetence and regeneration potential of the dental pulp and its surrounding apical tissues have been investigated extensively in the field of endodontics. While research on the role of non-coding RNAs in these tissues is still in its infancy, it is envisioned that improved understanding of the regulatory function of ncRNAs in pulpal and periapical immune response will help prevent or treat endodontic disease. Of particular importance is the role of these RNAs in regenerating the dentin-pulp complex. In this review, we highlight recent progress on the role of non-coding RNAs in the immune response to endodontic infection as well as the repair and regenerative response to injury.

Introduction

Endodontics is the branch of dentistry concerned with the morphology, physiology and pathology of the human dental pulp and periradicular tissues (the tissues surrounding the root of the tooth). The etiology for endodontic disease (i.e. pulpal and periapical disease) includes microbial infections from a carious lesions, inadequate (leaky) restorations, fractures and trauma. Dental caries is a highly prevalent disease. According to the Center for Disease Control the prevalence of dental caries in youth aged 2–19 years is 45.8% and the prevalence of untreated caries in the same age group is 13% [1], [2]. Even when the caries lesion is incipient and limited to the enamel, it evokes an immune response in the pulp [3]. As the carious infection progresses towards the pulp the immune/inflammatory response intensifies and can result in pulpal necrosis and periapical (aka periradicular) disease.

The cellular response to pulpal and periapical infection is mediated by several resident cells such as odontoblasts, fibroblasts and endothelial cells as well as immune cells which are recruited to the site of infection – macrophages, dendritic cells, neutrophils and lymphocytes [4]. The effector molecules released by these cells include cytokines, chemokines and proteases, among other pro-inflammatory mediators [5], [6]. The outcome of pulpal infection depends upon the extent of inflammation and may be regeneration and repair, or it may result in necrosis. The outcome of periapical infection is inflammation and bone resorption. A large number of studies have evaluated the role of the cellular and immune mediators in diseased dental pulps and periapical tissues [5], [7], [8], [9], [10], [11]. However, only a limited number of studies have examined the role of non-coding RNAs in endodontic disease.

Noncoding RNAs (ncRNAs) are RNAs that do not code for proteins. They can be classified based on subcellular localization (cytoplasmic versus nuclear), biological functions (housekeeping versus regulatory) or length (shorter or longer than 200 nt) [12]. The putative role of ncRNAs in the pulp and periapical tissues include odontogenic differentiation, regeneration, the immune response and bone resorption [13], [14], [15], [16]. Given the limited information on the role of ncRNAs in endodontic disease, this review focusses on only those ncRNAs on which substantial research has already been conducted.

Section snippets

MicroRNAs (miRNAs) in the pulpal response to infection

The role of miRNAs in the pulpal response to infection has been examined using both clinical biopsies and in vitro studies. The earliest report was from clinical biopsies of normal and inflamed pulps [17]. Thirty-three microRNAs were downregulated and only 3 were upregulated in the inflamed pulps as compared to normal pulps [17]. Given that miRNAs are negative regulators, decreased expression of a miRNA results in an increased stability or translation of their target messenger RNA. The miRNAs

Long noncoding RNA in endodontic Infections

In addition to microRNAs, the Human Genome Organization (HUGO) lists several other ncRNAs, namely: long non-coding RNAs, transfer RNAs, small nucleolar RNAs, ribosomal RNAs, small nuclear RNAs, piwi-interacting clusters, vault RNAs, Ro60-associated Y and small NF90 (ILF3) associated RNAs [28], [32]. Except for long non-coding RNAs, the role of these other ncRNAs in the pathogenesis of endodontic disease has not been elucidated as yet.

Long non-coding RNAs (lncRNAs) are non-protein coding

Circular RNA in endodontal diseases

In another DPSC microarray study, the global expression of circular RNAs (circRNAs) was analyzed to elucidate its role during odontogenesis [42]. In this study, human DPSCs were cultured for 14 days before RNA was extracted for microarray analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) validation. A total of 187 circRNAs were differentially expressed in DPSCs during odontogenic differentiation. Furthermore, bioinformatic analysis of the expression data

Conclusion

The role of ncRNAs in biological processes remains to be clarified as knowledge in this field is still in its infancy; however, their potential use in dentistry, particularly in the field of endodontics, can be envisioned already. With the current impetus in preserving pulp tissue [43] and in maintaining the tooth in the oral cavity [44], understanding the mechanisms governing the health and disease of the pulp and the periapical tissues cannot be more timely. The putative regulatory function

Conflict of interest

We (Drs. Johnah Galicia and Asma Khan), the authors of this manuscript have no conflict of interest to declare.

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