Bone morphogenetic protein-2 as a novel biomarker for refractory chronic rhinosinusitis with nasal polyps

Abstract

Background: Bone morphogenetic proteins (BMPs), which are members of the TGF-beta superfamily, regulate bone remodeling by stimulating osteoblasts and osteoclasts. Although the association between osteitis and poor surgical outcomes is well known in patients with chronic rhinosinusitis (CRS), BMPs have not been fully investigated as potential biomarkers for the prognosis of CRS. Objective: Our aim was to investigate the role of BMPs in osteitis in patients with CRS with nasal polyps (NPs) (CRSwNPs), as well as associations between BMPs and inflammatory markers in sinonasal tissues from patients with CRSwNP. Methods: We investigated the expression of 6 BMPs (BMP-2, BMP-4, BMP-6, BMP-7, BMP-9, and BMP-10) and their cellular origins in NPs of human subjects by using immunohistochemistry and ELISA of NP tissues. Exploratory factor analysis was performed to identify associations between BMPs and inflammatory markers. Air-liquid interface cell culture of human nasal epithelial cells was performed to evaluate the induction of the epithelial-mesenchymal transition by BMPs. Results: Of the 6 BMPs studied, BMP-2 and BMP-7 were associated with refractoriness. Only BMP-2 concentrations were higher in patients with severe osteitis and advanced disease extent according to the computed tomography findings. Eosinophils and some macrophages were identified as cellular sources of BMP-2 in immunofluorescence analysis. An in vitro experiment revealed that BMP-2 induced epithelialmesenchymal transition in air-liquid interface-cultured human nasal epithelial cells, particularly in a T(H)2 milieu. Conclusion: BMP-2 could reflect the pathophysiology of mucosa and bone remodeling and may be a novel biomarker for refractory CRSwNP.