Allergy Asthma Immunol Res.  2020 Mar;12(2):306-321. 10.4168/aair.2020.12.2.306.

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

Affiliations
  • 1Obstructive Upper airway Research (OUaR) Laboratory, Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea. charlie@snu.ac.kr
  • 2Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
  • 3Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  • 4Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Korea.
  • 5Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul, Korea.

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.

Keyword

Chronic; sinusitis; nose; nasal polyps; eosinophilia; osteogenesis; IL-13; RUNX2 protein; mouse; animal models

MeSH Terms

Animals
Computational Biology
Core Binding Factor Alpha 1 Subunit
Enterotoxins
Eosinophilia
Eosinophils*
Fluorescent Antibody Technique
Gene Expression
Humans
Immunohistochemistry
Interleukin-13
Interleukins
Mice
Models, Animal
Mucous Membrane
Nasal Polyps*
Nose
Osteitis
Osteoblasts
Osteoclasts
Osteogenesis
Osteonectin
Ovalbumin
Polymerase Chain Reaction
Sinusitis
Transcription Factors
Transcriptome
Core Binding Factor Alpha 1 Subunit
Enterotoxins
Interleukin-13
Interleukins
Osteonectin
Ovalbumin
Transcription Factors
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