Dawei Wu1,2, Angela L Nocera1, Sarina K Mueller1,3, Kristen Finn1, Towia A Libermann4, Benjamin S Bleier1. 1. From the Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, U.S.A. 2. Department of Otolaryngology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. 3. Department of Otolaryngology, University of Erlangen -Nuremberg, Erlangen, Germany. 4. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School Boston, Boston, Massachusetts, U.S.A.
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.
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.
Authors: Madison J Malfitano; Griffin D Santarelli; Mark Gelpi; William C Brown; Wesley H Stepp; Stephen Hernandez; Adam J Kimple; Brian D Thorp; Adam M Zanation; Charles S Ebert Journal: Am J Rhinol Allergy Date: 2020-07-13 Impact factor: 2.467