Differing Roles for TGF-β/Smad Signaling in Osteitis in Chronic Rhinosinusitis with and without Nasal Polyps

Abstract

Background Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP) is reported to involve different inflammatory processes in sinonasal mucosa and bone tissue, and these processes remain uncharacterized. Objective We aimed to investigate the molecular mechanisms of osteitis in Chinese patients with CRS to better understand the pathogenesis of CRS. Methods The study included 10 controls, 16 patients with CRSsNP, and 23 patients with CRSwNP. Ethmoid bone tissue samples were evaluated by histologic examination. Quantitative real-time reverse transcription polymerase chain reaction was used to assess expression of transforming growth factor (TGF) β1, TGF-β receptor I and II, Smad2, and Smad3. Immunohistochemical examination of osteoblast expression of TGF-β1, TGF-β receptor I and II, phosphorylated (p) Smad2, and p-Smad3 in ethmoid bone tissue was also performed. Results The histopathologic evaluation of ethmoid sinus bone tissue showed that eosinophils had infiltrated the periosteum and induced TGF-β1 expression, periosteal thickening, increased osteoblast activity, and neo-osteogenesis. Messenger RNA levels of TGF-β1, TGF-β receptor I, and Smad3 in CRSwNP ethmoid bone tissues were significantly higher than those in ethmoid bone tissues of patients with CRSsNP and the controls. Immunohistochemical staining showed that TGF-β1, TGF-β receptor I, p-Smad2, and p-Smad3 protein expression was upregulated in patients with CRSwNP, consistent with the corresponding messenger RNA levels. Conclusion Different signaling pathways are involved in osteitis in CRS and are activated by the TGF-β/Smad signaling pathway in CRSwNP versus the TGF-β/Smad-independent signaling pathway in CRSsNP. Eosinophil infiltration of the periosteum, along with TGF-β1 expression, in CRSwNP indicates that eosinophils may play an important role in the bone remodeling process in CRSwNP.