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

Roza KhalmuratovaObstructive Upper airway Research (OUaR) Laboratory, Department of Pharmacology, Seoul National University College of Medicine, Seoul, Republic of KoreaHyun‐Woo ShinObstructive Upper airway Research (OUaR) Laboratory, Department of Pharmacology, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea; Ischemic/hypoxic disease institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: [email protected]Dae Woo KimDepartment of Otorhinolaryngology-Head and Neck Surgery, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: [email protected]Jong‐Wan ParkObstructive Upper airway Research (OUaR) Laboratory, Department of Pharmacology, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea; Ischemic/hypoxic disease institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea

2019en

ABI

Annotatsiya

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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DOI: 10.1016/j.ebiom.2019.07.035

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