Osteitis is associated with dysregulated pro‐osteoblastic activity in patients with nasal polyps

Abstract

Objectives/Hypothesis The overlying inflammatory mucosa plays a crucial role in the initiation of osteitis; however, the molecular mechanism is unclear. The objective of this study was to explore the bone morphogenetic protein (BMP) pathway and to correlate the expression of key signaling molecules with the degree of osteitis in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Study Design Prospective experimental analysis. Methods This was an institutional review board–approved study in which mucosal samples were obtained from sites of osteitis in CRSwNP and compared to nonosteitic healthy controls (n = 10/group). Protein expression of key BMP pathway was quantified by aptamer‐based protein array and confirmed by a set of selected mRNA analyses. Degree of osteitis was assessed using both Kennedy Osteitis Score and Global Osteitis Score (GOS). Results Pro‐osteoblastic expression of BMP7 (fold change [FC] = −1.18, P = .017) and BMP9 (FC = −1.32, P = .023), their receptors, BMP receptor type‐1A (BMPR1A) (FC = −2.56, P = .005) and BMP receptor type‐2 (FC = −1.28, P = .022), and two enhancers of BMP signaling pathway, the repulsive guidance molecule domain family member B (FC = −1.13, P = .008) and the chordin‐like protein 1 (FC = −1.18, P = .027), were all significantly downregulated in CRSwNP. Conversely, the pro‐osteoclastic factor, tartrate‐resistant acid phosphatase type 5 (ACP5) (FC = 2.36, P = .001), was significantly increased in CRSwNP. GOS was inversely correlated with levels of BMP7 (r = −0.684, P = .005) and BMPR1A (r = −0.864, P = .005) and positively correlated with levels of ACP5 (r = 0.815, P = .004). The FCs among the proteins studied significantly and positively correlated with the FCs of their mRNA expression (r = 0.908, P = .002). Conclusions Downregulated pro‐osteoblastic mucosal BMP signaling is strongly and significantly associated with increased osteitis in CRSwNP. Level of Evidence NA Laryngoscope, 129:E102–E109, 2019

International consensus statement on allergy and rhinology: rhinosinusitis 2021

“…Growth differentiation factor 5 (GDF5), a member of the BMP family, was found to be upregulated in osteitic bone 671 . Additionally, Wu et al 672 identified that downregulation of pro‐osteoblastic BMP signaling correlates to increased neo‐osteogenesis in CRSwNP patients. Lastly, Kong et al 673 correlated upregulation of receptor activator nuclear factor κB ligand (RANKL) to degree of neo‐osteogenesis, and noted that blocking RANKL in a mouse model of CRS resulted in protection from mucosal inflammation and osteitis.…”

A Comparison of Sphenoid Sinus Osteoneogenesis in Aspirin-Exacerbated Respiratory Disease

“…7 However, a recent study by Wu et al examined the effect of bone morphogenetic protein (BMP) dysregulation on osteitic changes in CRS and demonstrated that dysregulated bone turnover may be the underlying factor to the bone thickening. 9 The presence and degree of osteitic thickening are significant as they correlate to more severe disease and create an unclear picture of prognostic outcomes following surgical intervention. 7,9,10 The more severe disease form, CRS with polyps, is associated with greater neo-osteogenesis and is a correlate of disease severity as these patients exhibit higher Lund-MacKay CT scores.…”

“…9 The presence and degree of osteitic thickening are significant as they correlate to more severe disease and create an unclear picture of prognostic outcomes following surgical intervention. 7,9,10 The more severe disease form, CRS with polyps, is associated with greater neo-osteogenesis and is a correlate of disease severity as these patients exhibit higher Lund-MacKay CT scores. 10 AFS is a derivative of CRS with polyps characterized by a Type I hypersensitivity reaction with the presence of eosinophilic mucin and fungi within the sinus.…”

Crosstalk Between Mucosal Inflammation and Bone Metabolism in Chronic Rhinosinusitis

“…In a more recent study, Wu et al [46] assessed mucosal samples obtained from sites of osteitic bone in 10 patients with CRSwNP and 10 healthy controls. The authors found that pro-osteoblastic expression of BMP-7, BMP-9, and their receptors (BMPR1A and BMPR2) were downregulated in CRSwNP, indicating a generalized decrease in pro-osteoblastic activity.…”