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Published on: June 13, 2016
MicroRNA Expression Profiles in External Cervical Resorption
Mary T Pettiette1, Shaoping Zhang2, Antonio J Moretti3
1Department of Endodontics, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
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.
Insights
External cervical resorption (ECR) has unique microRNA (miRNA) expression profiles compared to chronic periodontitis. These differentially expressed miRNAs target genes involved in inflammation, immunity, and mineralized tissue metabolism.
Area of Science:
- Oral Biology
- Molecular Biology
- Biochemistry
Background:
- External cervical resorption (ECR) presents diagnostic and therapeutic challenges due to unknown etiology and pathogenesis.
- MicroRNA (miRNA) expression patterns in ECR lesions remain largely uncharacterized.
Purpose of the Study:
- To characterize miRNA expression in human ECR tissues.
- To identify potential messenger RNA (mRNA) targets and associated biological pathways for ECR.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) array analysis of 88 miRNAs in ECR, chronic periodontitis (CP), and control tissues.
- Bioinformatic analyses (miRWalk, KEGG pathways) to predict mRNA targets and signaling pathways.
- Statistical analysis (Student t test) to identify differentially expressed miRNAs.
Main Results:
- Three miRNAs (miR-20a-5p, miR-210-3p, miR-99a-4p) were downregulated, and one (miR-122-5p) was upregulated in ECR.
- ECR and CP exhibited distinct miRNA expression profiles, with 3 differentially expressed miRNAs identified between them.
- Predicted pathways modulated by miRNAs in ECR include glycosaminoglycan biosynthesis, mineral absorption, and insulin signaling.
Conclusions:
- ECR exhibits unique miRNA expression profiles compared to CP, suggesting distinct pathobiology.
- Differentially expressed miRNAs in ECR are predicted to target genes regulating inflammation, immunity, and mineralized tissue metabolism.
- This study provides a foundation for understanding the molecular mechanisms underlying ECR.
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