Dataset Information

Evaluation of Neo-Osteogenesis in Eosinophilic Chronic Rhinosinusitis Using a Nasal Polyp Murine Model.

ABSTRACT: PURPOSE:Osteitis refers to the development of new bone formation and remodeling of bone in chronic rhinosinusitis (CRS) patients; it is typically associated with eosinophilia, nasal polyps (NPs), and recalcitrant CRS. However, the roles of ossification in CRS with or without NPs remain unclear due to the lack of appropriate animal models. Thus, it is necessary to have a suitable animal model for greater advances in the understanding of CRS pathogenesis. METHODS:BALB/c mice were administered ovalbumin (OVA) and staphylococcal enterotoxin B (SEB). The numbers of osteoclasts and osteoblasts and bony changes were assessed. Micro computed tomography (micro-CT) scans were conducted to measure bone thickness. Immunofluorescence, immunohistochemistry, and quantitative polymerase chain reaction were performed to evaluate runt-related transcription factor 2 (RUNX2), osteonectin, interleukin (IL)-13, and RUNX2 downstream gene expression. Gene set enrichment analysis was performed in mucosal tissues from control and CRS patients. The effect of resveratrol was evaluated in terms of osteogenesis in a murine eosinophilic CRS NP model. RESULTS:The histopathologic changes showed markedly thickened bones with significant increase in osteoblast numbers in OVA/SEB-treated mice compared to the phosphate-buffered saline-treated mice. The structural changes in bone on micro-CT were consistent with the histopathological features. The expression of RUNX2 and IL-13 was increased by the administration of OVA/SEB and showed a positive correlation. RUNX2 expression mainly co-localized with osteoblasts. Bioinformatic analysis using human CRS transcriptome revealed that IL-13-induced bony changes via RUNX2. Treatment with resveratrol, a candidate drug against osteitis, diminished the expression of IL-13 and RUNX2, and the number of osteoblasts in OVA/SEB-treated mice. CONCLUSIONS:In the present study, we found the histopathological and radiographic evidence of osteogenesis using a previously established murine eosinophilic CRS NP model. This animal model could provide new insights into the pathophysiology of neo-osteogenesis and provide a basis for developing new therapeutics.

SUBMITTER: Khalmuratova R

PROVIDER: S-EPMC6997277 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Evaluation of Neo-Osteogenesis in Eosinophilic Chronic Rhinosinusitis Using a Nasal Polyp Murine Model.

Khalmuratova Roza R Lee Mingyu M Park Jong Wan JW Shin Hyun Woo HW

Allergy, asthma & immunology research 20200301 2

<h4>Purpose</h4>Osteitis refers to the development of new bone formation and remodeling of bone in chronic rhinosinusitis (CRS) patients; it is typically associated with eosinophilia, nasal polyps (NPs), and recalcitrant CRS. However, the roles of ossification in CRS with or without NPs remain unclear due to the lack of appropriate animal models. Thus, it is necessary to have a suitable animal model for greater advances in the understanding of CRS pathogenesis.<h4>Methods</h4>BALB/c mice were ad ...[more]

PMID: 32009324

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Project description:Background: Alternative polyadenylation (APA) is emerging as a widespread mechanism of gene regulation. The usage of APA sites allows a single gene to encode multiple mRNA transcripts with different 3'-untranslated region (3'UTR) lengths. Many disease processes reflect the importance of the regulation of APA site switching. The objective of this study was to explore the profiling of tandem APA sites in nasal polyps compared with nasal uncinate process mucosa. Methods: Sequencing of APA sites (SAPAS) based on second-generation sequencing technology was undertaken to investigate the use of tandem APA sites and identify gene expression patterns in samples from the nasal polyps and nasal uncinate process mucosa of two patients with chronic rhinosinusitis with nasal polyps. The findings of the SAPAS analysis were validated via quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Results: First, the results showed a switching of 3'UTR lengths in nasal polyps compared with nasal uncinate process mucosa. From the two patients, 105 overlapping genes in the nasal polyps were switched to distal poly(A) sites, and 90 such genes were switched to proximal poly(A) sites. Several Gene Ontology terms were enriched in the list of genes with switched APA sites, including transcription regulation, cell cycle, apoptosis, and metabolism. Second, we detected genes that showed differential expression with at least a 3-fold difference between nasal polyp tissue and nasal uncinate process mucosa. Between the two sample types, 627 genes exhibited differential expression. The qRT-PCR results confirmed our SAPAS results. Conclusion: APA site-switching events of 3'UTRs are prevalent in nasal polyp tissue, and the regulation of gene expression mediated by APA may play an important role in the formation and persistence of nasal polyps. Our results may provide new insights into the possible pathophysiologic processes involved in nasal polyps. Investigate the use of tandem APA sites of 3'ends of mRNAs using second-generation sequencing technology.

Dataset Information

Evaluation of Neo-Osteogenesis in Eosinophilic Chronic Rhinosinusitis Using a Nasal Polyp Murine Model.

Publications

Evaluation of Neo-Osteogenesis in Eosinophilic Chronic Rhinosinusitis Using a Nasal Polyp Murine Model.

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