Bone morphogenetic protein-2 as a novel biomarker for refractory chronic rhinosinusitis with nasal polyps - 04/08/21
, Dae Woo Kim, MD, PhD a, ⁎, ‡ Abstract |
Background |
Bone morphogenetic proteins (BMPs), which are members of the TGF-β 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 epithelial-mesenchymal transition in air-liquid interface–cultured human nasal epithelial cells, 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.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Nasal polyp, bone morphogenetic proteins, sinusitis, osteitis, biomarker
Abbreviations used : ALI, AUC, BMP, BMPR1A, CRS, CRSwNP, CT, EFA, EMBP, EMT, GOSS, HNE, hNEC, LM CT, NP, r, ROC, RUNX2, TEER, UP
Plan
| Supported by the National Research Foundation of Korea (grant NRF-2019R1A2C2087170 [to D.W.K.] and grant 2020R1A4A2002903 [to H.W.S.]), the Seoul Metropolitan Government Seoul National University Boramae Medical Center (focused clinical research grant-in-aid 03-2019-1 [to D.W.K.]), and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (grant HI17C1669 to [H.W.S.]). |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 148 - N° 2
P. 461 - août 2021 Retour au numéro
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