Transcriptome analysis (RNA-seq) of bone remodeling in patients with chronic rhinosinusitis with nasal polyposis

Abstract

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease affecting the nasal cavities and paranasal sinuses, which lasts more than 12 weeks without complete resolution of symptoms, and it can be clinically divided in CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). It is well known for being accompanied with bone remodeling radiologically. The bone remodeling which often accompanies CRS is related to unsatisfactory surgical results and frequent recurrence, but the mechanism of the bone remodeling has not been revealed yet. This study aimed at investigating the mechanism of bone remodeling in CRS using transcriptome analysis (RNA-seq). 6 therapy resistant CRSwNP patients who underwent endoscopic sinus surgery (ESS) and had bone remodeling radiologically were enrolled. Con-trols were the cases of endoscopic repair of blow out fracture (n = 3) and cerebrospinal fluid leak (n = 1). Bulla ethmoidalis was taken during ESS. The bone tissues were dissected from mucosa and stored until RNA extraction. Total RNA was extracted with the Trizol method and the transcriptome (RNA-seq) analysis was performed. The author found 255 differentially expressed genes with |fold change| ≥ 2 and raw p-value < 0.05. 134 genes were up-regulated and 91 were down-regulated. Osteoblastic activity related genes were 16 (11 were up-regulated and 5 were down-regulated) and osteoclastic activity related genes were 18 (15 were up-regulated and 3 were down-regulated). 6 genes were related to osteoblastic and osteoclastic activity on both sides. On the analysis of the transcriptomic profiles, this study showed that 255 genes were differentially expressed in CRSwNP patients compared to control patients. This study also revealed the 28 specific genes associated with osteoblastic and osteoclastic activity which can affect bone remodeling in CRSwNP. On the gene set enrichment analysis, the transcriptomic change was more associated with inflammatory process than with direct process related to the osteoblastogenesis or osteoclastogenesis. More studies will be needed to validate the effect of these candidate genes to bone remodeling in CRS. These consecutive studies might provide a novel therapeutic approach to target the genes in the treatment of recalcitrant CRS.