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

Abstract Background Bone morphogenetic proteins (BMPs), members of the transforming growth factor-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 This study investigated the role of BMPs in osteitis in CRS with nasal polyp (NP) (CRSwNP) patients, as well as associations between BMPs and inflammatory markers in sinonasal tissues from CRSwNP patients. 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 using immunohistochemistry and enzyme-linked immunosorbent assays of NP tissues. Exploratory factor analysis was performed to identify associations between BMPs and inflammatory markers. Air-liquid interface (ALI) cell culture of human nasal epithelial cells (hNECs) was performed to evaluate the induction of the epithelial–mesenchymal transition (EMT) 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 based on 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 EMT in ALI-cultured hNECs, particularly in a Th2 milieu. Conclusion BMP-2 could reflect the pathophysiology of mucosa and bone remodeling, and may be a novel biomarker for refractory CRSwNP.