Elsevier

Journal of Endodontics

Volume 45, Issue 9, September 2019, Pages 1106-1113.e2
Journal of Endodontics

Clinical Research
MicroRNA Expression Profiles in External Cervical Resorption

https://doi.org/10.1016/j.joen.2019.06.001Get rights and content

Abstract

Introduction

External cervical resorption (ECR) has been challenging for its diagnosis, prevention, and treatment. Its etiology and pathogenesis are largely unknown. This study characterized microRNA (miRNA) expression patterns of human tissues from ECR lesions and identified potential messenger RNA targets and pathways.

Methods

Granulomatous tissues from ECR (n = 5) and their adjacent nonaffected asymptomatic gingival connective tissues (n = 5) were collected. Similarly, chronic periodontitis (CP) and control samples were collected (n = 3). Quantitative reverse transcription polymerase chain reaction array analysis compared the expression profiles of 88 miRNAs between diseases. Differentially expressed miRNAs were identified using the Student t test. Bioinformatics for messenger RNA (miRWalk) and KEGG pathway analyses were performed to identify predicted target genes and biological/cellular functions and signaling pathways.

Results

Three miRNAs (miR-20a-5p, miR-210-3p, and miR-99a-4p) were significantly down-regulated and 1 miRNA (miR-122-5p) was significantly up-regulated in ECR (P < .05). One up-regulated and 1 down-regulated miRNA reached the significance threshold in CP. A comparison of miRNA expression in ECR and CP identified 3 differentially expressed miRNAs, indicating differences in disease pathobiology. Inflammation-associated Wnt, PI3K-Akt, mitogen-activated protein kinases signaling, and bone formation–associated transforming growth factor beta pathways were identified and predicted to be modulated by differentially expressed miRNAs in both ECR and CP. Biological processes unique to each disease entity were identified, such as T- and B-cell receptor signaling pathways, osteoclast differentiation, and extracellular matrix–receptor interaction for CP. Glycosaminoglycan biosynthesis, mineral absorption, and insulin signaling pathways for ECR were identified.

Conclusions

This proof-of-principle in vivo study indicated that ECR has both common and unique miRNA expression profiles in comparison with CP, which are predicted to target genes regulating inflammation, immunity, and metabolism of mineralized tissues.

Section snippets

Study Participants and Sample Collection

This was a single-center pilot study that evaluated the miRNA levels in individuals with ECR or CP. Granulomatous tissue (test) samples and clinically asymptomatic or clinically healthy gingival biopsy (control) samples were collected from participants with ECR or CP at the time of the surgical treatment. In total, 8 participants (5 with ECR and 3 with CP) were recruited from a pool of individuals seeking dental treatment at the University of North Carolina at Chapel Hill School of Dentistry’s

Results

Demographic, clinical, and pulp diagnosis data of the study participants are shown in Supplemental Table S1 (available online at www.jendodon.com). All ECR-involved teeth were either maxillary or mandibular anterior teeth. The teeth with ECR, having had a history of trauma, all had the diagnosis of necrotic pulp. Interestingly, the cases of unknown etiology for ECR had vital pulp status. Figure 1 depicts radiographic evidence of 2 ECR-involved teeth (#6 and #24) from different patients. ECR

Discussion

In this report, we sought to uncover the potential role of miRNAs in ECR and CP, both of which are inflammatory diseases that possess unique pathogenicity. Clinically, ECR and CP have a common feature regarding the resorption of the adjacent hard tissues in which ECR affects the cementum and dentin and CP affects the alveolar bone. To our knowledge, this pilot study is the first to identify differential expression of miRNAs in ECR. By comparing the differentially regulated miRNA species in ECR

Acknowledgments

Supported in part by the American Association of Endodontists Foundation and the National Institutes of Health/National Institute of Dental and Craniofacial Research (grant nos. R21 DE026259-01A1, R01 DE027980, and R03 DE027147 to A.R.N.; R01 DE02105201A1 to S.N.; and 1K99DE027086 to S.Z.).

The authors deny any conflicts of interest related to this study.

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