Chronic rhinosinusitis osteoblasts differ in cellular properties from normal bone

Stevens, Patrick; Tessema, Belachew; Brown, Seth M.; Parham, Kourosh; Gronowicz, Gloria

doi:10.1002/alr.21434

Cited by 7 publications

(7 citation statements)

References 24 publications

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“…Serum eosinophilia has also been linked with P‐glycoprotein levels and radiographic osteitis scores 668 . Early studies investigating the role of osteoblasts in sinus neo‐osteogenesis demonstrated decreased osteoblast adhesion and proliferation, and increased bone mineralization in CRS osteoblasts compared to controls 669 . More recently, Khalmuratova et al 670 reported an association between RUNX2 expression, a key osteoblast differentiation transcription factor, and neo‐osteogenesis, that was further activated by the proinflammatory cytokines IL‐13 and IL‐17A.…”

Section: Chronic Rhinosinusitis Without Nasal Polyps (Crssnp)mentioning

confidence: 99%

International consensus statement on allergy and rhinology: rhinosinusitis 2021

Orlandi

Kingdom

Smith

et al. 2021

Int Forum Allergy Rhinol

530

479

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I. Executive Summary Background The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS.

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Section: Chronic Rhinosinusitis Without Nasal Polyps (Crssnp)mentioning

confidence: 99%

International consensus statement on allergy and rhinology: rhinosinusitis 2021

Orlandi

Kingdom

Smith

et al. 2021

Int Forum Allergy Rhinol

530

479

View full text Add to dashboard Cite

show abstract

“…Nonetheless, the severity of neoosteogenesis is considered as one of the predictors of postoperative re-stenosis, requiring the Draf III or modified Lothrop procedures, which involve the most challenging frontal sinus surgeries [6]. Notably, there are phenotypic differences in adhesion and mineralisation between osteoblasts in CRS patients when compared with control subjects [7]. These differences suggest that identification of the immunological and molecular mechanisms of osteoblast activation can be used to help understand neoosteogenesis and treat recalcitrant CRS.…”

Section: Introductionmentioning

confidence: 99%

Interleukin (IL)-13 and IL-17A contribute to neo-osteogenesis in chronic rhinosinusitis by inducing RUNX2

et al. 2019

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Background There is increasing evidence supporting the impact of neoosteogenesis in the pathophysiology of chronic rhinosinusitis (CRS), especially in the recalcitrant group of patients. Runt-related transcription factor 2 (RUNX2), a member of the RUNX family, controls osteoblast differentiation and bone formation. However, the role and regulation of RUNX2 in CRS patients with neoosteogenesis remain unclear. The aim of the study is to determine the role of RUNX2 in neoosteogenesis of CRS patients. Methods Sinonasal bone and overlying mucosa samples were obtained from CRS patients with or without neoosteogenesis ( n = 67) and healthy controls ( n = 11). Double immunofluorescence, immunohistochemistry, and immunoblotting were used to evaluate RUNX2 expression in CRS patients with and without neoosteogenesis. In addition, the osteogenic activity of pro-inflammatory cytokines was examined by measuring alkaline phosphatase (ALP) activity and bone mineralisation in vitro . Findings RUNX2 was highly expressed in osteoblasts of CRS patients with neoosteogenesis compared with tissues from control subjects and those with CRS without neoosteogenesis. Mucosal extracts from CRS patients with neoosteogenesis showed increased RUNX2 expression and ALP activity in C2C12 cells, whereas those from patients without neoosteogenesis did not. Expression of interleukin (IL)-13 and IL-17A was upregulated in CRS patients with neoosteogenesis. ALP activity and Alizarin Red staining showed IL-13 and IL-17A dose-dependent osteoblast differentiation and mineralisation in vitro . Interpretation These findings suggested that IL-13- or IL-17A-induced RUNX2 contributed to new bone formation in CRS patients through its effect on the activity of osteoblasts. RUNX2 may be a novel target for preventing neoosteogenesis in CRS patients.

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“…Primary bone cells of CRSwNP were isolated as previously described 29,30 . Briefly, nasal poly‐ and soft tissues of sinus bone tissues were stripped using forceps.…”

Section: Methodsmentioning

confidence: 99%

Eosinophil‐derived interferon‐γ drives transmembrane protein 119–induced new bone formation in chronic rhinosinusitis with nasal polyps

Jin

Lee

et al. 2022

Int Forum Allergy Rhinol

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Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory sinonasal disease characterized by eosinophilic infiltration and new bone formation. These changes indicate the severity and prognosis of CRSwNP and may be closely linked to each other. Methods We performed RNA sequencing to screen specific osteogenic molecules and validated transmembrane protein 119 (TMEM119) expression by quantitative polymerase chain reaction (qPCR) and immunohistochemistry analyses. TMEM119 knockdown was performed to observe the downregulation of bone mineralization. We validated the bone‐forming activity of interferon‐γ (IFN‐γ) and its signaling pathways in cultured primary sinus bone cells. Cellular sources of IFN‐γ were identified using immunohistochemistry and immunofluorescence analyses. Interleukin‐4–eosinophil–IFN‐γ axis and the effect of dupilumab were investigated in Eol‐1 cells. Results We observed elevated IFN‐γ levels and eosinophils in the nasal fluid and predominantly eosinophil‐derived IFN‐γ in the sinus mucosa of patients with CRSwNP. TMEM119 expression and bone‐forming activities were increased in the osteitic and primary sinus bone cells of CRSwNP. IFN‐γ treatment enhanced bone mineralization and TMEM119 expression via signal transducer and activator of transcription 1 (STAT1) signaling. Moreover, TMEM119 knockdown inhibited sinus bone cell mineralization and dupilumab attenuated IFN‐γ secretion by IL4‐stimulated Eol‐1 cells. Conclusion Eosinophil‐derived IFN‐γ promotes the bone‐forming activities of sinus bone cells via the STAT1–TMEM119 signaling pathway. Interleukin‐4–eosinophil–IFN‐γ axis may be crucial for TMEM119‐mediated new bone formation in CRSwNP.

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Chronic rhinosinusitis osteoblasts differ in cellular properties from normal bone

Cited by 7 publications

References 24 publications

International consensus statement on allergy and rhinology: rhinosinusitis 2021

International consensus statement on allergy and rhinology: rhinosinusitis 2021

Interleukin (IL)-13 and IL-17A contribute to neo-osteogenesis in chronic rhinosinusitis by inducing RUNX2

Eosinophil‐derived interferon‐γ drives transmembrane protein 119–induced new bone formation in chronic rhinosinusitis with nasal polyps

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