Clin Exp Otorhinolaryngol.  2021 Feb;14(1):43-49. 10.21053/ceo.2020.00416.

Crosstalk Between Mucosal Inflammation and Bone Metabolism in Chronic Rhinosinusitis

Affiliations
  • 1Obstructive Upper airway Research (OUaR) Laboratory, Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea
  • 2Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea
  • 3Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Korea
  • 4Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
  • 5Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul, Korea

Abstract

Chronic rhinosinusitis (CRS) is a multifactorial and highly heterogeneous upper airway disease that affects approximately 12% of the general population. There is increasing evidence supporting the impact of osteitis on the pathophysiology of CRS. Osteitis is frequently observed in patients with CRS, and is associated with severe sinonasal inflammation and recalcitrant cases. The overlying inflammatory sinonasal mucosa plays a critical role in the initiation of osteitis; however, the underlying molecular mechanisms and functional significance remain unclear. Increasingly many studies have suggested that immune cells play a crucial role in the bone remodeling process in CRS. The purpose of this review is to summarize the current state of knowledge regarding the specific role of sinonasal inflammation in bone remodeling in CRS patients.

Keyword

Osteitis; Chronic Rhinosinusitis; Inflammation; Osteoblasts; Osteoclasts; Cytokine

Figure

  • Fig. 1. The interplay between immune cells and bone in chronic rhinosinusitis (CRS). Immune cells are involved in shaping the CRS pathophysiology and directly impact osteogenic cells. IL-13 is a pleiotropic type 2 cytokine that contributes to bone remodeling in patients with eosinophilic CRS through its effects on the activity of osteoblasts. IL-17A is a cytokine secreted primarily by Th17 cells that regulates the activity of osteoblasts in non-eosinophilic CRS. IL, interleukin; Th, T helper; ILC2, type 2 innate lymphoid cells.


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Reference

1. Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, et al. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology. 2012; Mar. 50(1):1–12.
Article
2. Hamilos DL. Chronic rhinosinusitis: epidemiology and medical management. J Allergy Clin Immunol. 2011; Oct. 128(4):693–707.
Article
3. Schleimer RP. Immunopathogenesis of chronic rhinosinusitis and nasal polyposis. Annu Rev Pathol. 2017; Jan. 12:331–57.
Article
4. Khalmuratova R, Park JW, Shin HW. Immune cell responses and mucosal barrier disruptions in chronic rhinosinusitis. Immune Netw. 2017; Feb. 17(1):60–7.
Article
5. Akdis CA, Bachert C, Cingi C, Dykewicz MS, Hellings PW, Naclerio RM, et al. Endotypes and phenotypes of chronic rhinosinusitis: a PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2013; Jun. 131(6):1479–90.
6. Van Zele T, Claeys S, Gevaert P, Van Maele G, Holtappels G, Van Cauwenberge P, et al. Differentiation of chronic sinus diseases by measurement of inflammatory mediators. Allergy. 2006; Nov. 61(11):1280–9.
Article
7. Brescia G, Zanotti C, Parrino D, Barion U, Marioni G. Nasal polyposis pathophysiology: endotype and phenotype open issues. Am J Otolaryngol. 2018; Jul-Aug. 39(4):441–4.
Article
8. Cao PP, Li HB, Wang BF, Wang SB, You XJ, Cui YH, et al. Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese. J Allergy Clin Immunol. 2009; Sep. 124(3):478–84.
Article
9. Kim SJ, Lee KH, Kim SW, Cho JS, Park YK, Shin SY. Changes in histological features of nasal polyps in a Korean population over a 17-year period. Otolaryngol Head Neck Surg. 2013; Sep. 149(3):431–7.
Article
10. Tikaram A, Prepageran N. Asian nasal polyps: a separate entity. Med J Malaysia. 2013; Dec. 68(6):445–7.
11. Cho SW, Kim DW, Kim JW, Lee CH, Rhee CS. Classification of chronic rhinosinusitis according to a nasal polyp and tissue eosinophilia: limitation of current classification system for Asian population. Asia Pac Allergy. 2017; Jul. 7(3):121–30.
Article
12. Snidvongs K, Sacks R, Harvey RJ. Osteitis in chronic rhinosinusitis. Curr Allergy Asthma Rep. 2019; Mar. 19(5):24.
Article
13. Bhandarkar ND, Sautter NB, Kennedy DW, Smith TL. Osteitis in chronic rhinosinusitis: a review of the literature. Int Forum Allergy Rhinol. 2013; May. 3(5):355–63.
Article
14. Snidvongs K, Earls P, Dalgorf D, Sacks R, Pratt E, Harvey RJ. Osteitis is a misnomer: a histopathology study in primary chronic rhinosinusitis. Int Forum Allergy Rhinol. 2014; May. 4(5):390–6.
Article
15. Lee JT, Kennedy DW, Palmer JN, Feldman M, Chiu AG. The incidence of concurrent osteitis in patients with chronic rhinosinusitis: a clinicopathological study. Am J Rhinol. 2006; May-Jun. 20(3):278–82.
Article
16. Sacks PL, Snidvongs K, Rom D, Earls P, Sacks R, Harvey RJ. The impact of neo-osteogenesis on disease control in chronic rhinosinusitis after primary surgery. Int Forum Allergy Rhinol. 2013; Oct. 3(10):823–7.
Article
17. Snidvongs K, McLachlan R, Chin D, Pratt E, Sacks R, Earls P, et al. Osteitic bone: a surrogate marker of eosinophilia in chronic rhinosinusitis. Rhinology. 2012; Sep. 50(3):299–305.
Article
18. Georgalas C, Videler W, Freling N, Fokkens W. Global Osteitis Scoring Scale and chronic rhinosinusitis: a marker of revision surgery. Clin Otolaryngol. 2010; Dec. 35(6):455–61.
Article
19. Cho SH, Min HJ, Han HX, Paik SS, Kim KR. CT analysis and histopathology of bone remodeling in patients with chronic rhinosinusitis. Otolaryngol Head Neck Surg. 2006; Sep. 135(3):404–8.
Article
20. Biedlingmaier JF, Whelan P, Zoarski G, Rothman M. Histopathology and CT analysis of partially resected middle turbinates. Laryngoscope. 1996; Jan. 106(1 Pt 1):102–4.
Article
21. Giacchi RJ, Lebowitz RA, Yee HT, Light JP, Jacobs JB. Histopathologic evaluation of the ethmoid bone in chronic sinusitis. Am J Rhinol. 2001; May-Jun. 15(3):193–7.
Article
22. Bhandarkar ND, Mace JC, Smith TL. The impact of osteitis on disease severity measures and quality of life outcomes in chronic rhinosinusitis. Int Forum Allergy Rhinol. 2011; Sep-Oct. 1(5):372–8.
Article
23. Snidvongs K, McLachlan R, Sacks R, Earls P, Harvey RJ. Correlation of the Kennedy Osteitis Score to clinico-histologic features of chronic rhinosinusitis. Int Forum Allergy Rhinol. 2013; May. 3(5):369–75.
Article
24. Meng Y, Lou H, Wang C, Zhang L. Predictive significance of computed tomography in eosinophilic chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol. 2016; Aug. 6(8):812–9.
Article
25. Kong IG, Kim DK, Eun KM, Yang SK, Kim M, Oh H, et al. Receptor activator of nuclear factor κB ligand is a biomarker for osteitis of chronic rhinosinusitis. Int Forum Allergy Rhinol. 2020; Mar. 10(3):364–73.
Article
26. Florencio-Silva R, Sasso GR, Sasso-Cerri E, Simoes MJ, Cerri PS. Biology of bone tissue: structure, function, and factors that influence bone cells. Biomed Res Int. 2015; 2015:421746.
Article
27. Caetano-Lopes J, Canhao H, Fonseca JE. Osteoblasts and bone formation. Acta Reumatol Port. 2007; Apr-Jun. 32(2):103–10.
28. Metzger CE, Narayanan SA. The role of osteocytes in inflammatory bone loss. Front Endocrinol (Lausanne). 2019; May. 10:285.
Article
29. Ishino T, Yajin K, Takeno S, Furukido K, Hirakawa K. Establishment of osteoblast culture from human ethmoidal sinus. Auris Nasus Larynx. 2003; Feb. 30(1):45–51.
Article
30. Stevens PR, Tessema B, Brown SM, Parham K, Gronowicz G. Chronic rhinosinusitis osteoblasts differ in cellular properties from normal bone. Int Forum Allergy Rhinol. 2015; Feb. 5(2):124–31.
Article
31. Mehta V, Campeau NG, Kita H, Hagan JB. Blood and sputum eosinophil levels in asthma and their relationship to sinus computed tomographic findings. Mayo Clin Proc. 2008; Jun. 83(6):671–8.
Article
32. Gunel C, Feldman RE, Bleier BS. Osteitis is associated with P-glycoprotein overexpression in patients with chronic sinusitis without nasal polyps. Am J Rhinol Allergy. 2014; Mar-Apr. 28(2):99–102.
33. Miyake MM, Nocera A, Miyake MM. P-glycoprotein and chronic rhinosinusitis. World J Otorhinolaryngol Head Neck Surg. 2018; Aug. 4(3):169–74.
Article
34. Cheng YS, Bleier BS. Influence of P-glycoprotein function on chronic rhinosinusitis/nasal polyps pathophysiology. Adv Otorhinolaryngol. 2016; 79:38–47.
Article
35. Feldman RE, Lam AC, Sadow PM, Bleier BS. P-glycoprotein is a marker of tissue eosinophilia and radiographic inflammation in chronic rhinosinusitis without nasal polyps. Int Forum Allergy Rhinol. 2013; Aug. 3(8):684–7.
Article
36. Bleier BS, Nocera AL, Iqbal H, Hoang JD, Alvarez U, Feldman RE, et al. P-glycoprotein promotes epithelial T helper 2-associated cytokine secretion in chronic sinusitis with nasal polyps. Int Forum Allergy Rhinol. 2014; Jun. 4(6):488–94.
Article
37. Bleier BS, Singleton A, Nocera AL, Kocharyan A, Petkova V, Han X. P-glycoprotein regulates Staphylococcus aureus enterotoxin B-stimulated interleukin-5 and thymic stromal lymphopoietin secretion in organotypic mucosal explants. Int Forum Allergy Rhinol. 2016; Feb. 6(2):169–77.
38. Onoe Y, Miyaura C, Kaminakayashiki T, Nagai Y, Noguchi K, Chen QR, et al. IL-13 and IL-4 inhibit bone resorption by suppressing cyclooxygenase-2-dependent prostaglandin synthesis in osteoblasts. J Immunol. 1996; Jan. 156(2):758–64.
39. Silfversward CJ, Larsson S, Ohlsson C, Frost A, Nilsson O. Reduced cortical bone mass in mice with inactivation of interleukin-4 and interleukin-13. J Orthop Res. 2007; Jun. 25(6):725–31.
40. Silfversward CJ, Penno H, Frost A, Nilsson O, Ljunggren O. Expression of markers of activity in cultured human osteoblasts: effects of interleukin-4 and interleukin-13. Scand J Clin Lab Invest. 2010; Sep. 70(5):338–42.
41. Tuszynska A, Krzeski A, Postuba M, Paczek L, Wyczalkowska-Tomasik A, Gornicka B, et al. Inflammatory cytokines gene expression in bone tissue from patients with chronic rhinosinusitis: a preliminary study. Rhinology. 2010; Dec. 48(4):415–9.
Article
42. Wang M, Ye T, Liang N, Huang Z, Cui S, Li Y, et al. Differing roles for TGF-β/Smad signaling in osteitis in chronic rhinosinusitis with and without nasal polyps. Am J Rhinol Allergy. 2015; Sep-Oct. 29(5):e152–9.
Article
43. Gunel C, Bleier BS, Bozkurt G, Eliyatkin N. Microarray analysis of the genes associated with osteitis in chronic rhinosinusitis. Laryngoscope. 2017; Mar. 127(3):E85–90.
44. Jin L, Li X. Growth differentiation factor 5 regulation in bone regeneration. Curr Pharm Des. 2013; 19(19):3364–73.
Article
45. Sautter NB, Delaney KL, Hausman FA, Trune DR. Tissue remodeling gene expression in a murine model of chronic rhinosinusitis. Laryngoscope. 2012; Apr. 122(4):711–7.
Article
46. Wu D, Nocera AL, Mueller SK, Finn K, Libermann TA, Bleier BS. Osteitis is associated with dysregulated pro-osteoblastic activity in patients with nasal polyps. Laryngoscope. 2019; Mar. 129(3):E102–9.
Article
47. Oue S, Ramezanpour M, Paramasivan S, Miljkovic D, Cooksley CM, Bassiouni A, et al. Increased IL-13 expression is independently associated with neo-osteogenesis in patients with chronic rhinosinusitis. J Allergy Clin Immunol. 2017; Nov. 140(5):1444–8.
Article
48. Khalmuratova R, Lee M, Park JW, Shin HW. Evaluation of neo-osteogenesis in eosinophilic chronic rhinosinusitis using a nasal polyp murine model. Allergy Asthma Immunol Res. 2020; Mar. 12(2):306–21.
Article
49. Shi N, Zhang J, Chen SY. Runx2, a novel regulator for goblet cell differentiation and asthma development. FASEB J. 2017; Jan. 31(1):412–20.
Article
50. Khalmuratova R, Shin HW, Kim DW, Park JW. Interleukin (IL)-13 and IL-17A contribute to neo-osteogenesis in chronic rhinosinusitis by inducing RUNX2. EBioMedicine. 2019; Aug. 46:330–41.
Article
51. Komori T. Regulation of bone development and maintenance by Runx2. Front Biosci. 2008; Jan. 13:898–903.
Article
52. Jensen ED, Gopalakrishnan R, Westendorf JJ. Regulation of gene expression in osteoblasts. Biofactors. 2010; Jan-Feb. 36(1):25–32.
Article
53. Komori T. Regulation of bone development and extracellular matrix protein genes by RUNX2. Cell Tissue Res. 2010; Jan. 339(1):189–95.
Article
54. Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys. 2008; May. 473(2):139–46.
Article
55. Walsh MC, Choi Y. Biology of the RANKL-RANK-OPG system in immunity, bone, and beyond. Front Immunol. 2014; Oct. 5:511.
Article
56. Yeo L, Toellner KM, Salmon M, Filer A, Buckley CD, Raza K, et al. Cytokine mRNA profiling identifies B cells as a major source of RANKL in rheumatoid arthritis. Ann Rheum Dis. 2011; Nov. 70(11):2022–8.
Article
57. Ogasawara N, Poposki JA, Klingler AI, Tan BK, Hulse KE, Stevens WW, et al. Role of RANK-L as a potential inducer of ILC2-mediated type 2 inflammation in chronic rhinosinusitis with nasal polyps. Mucosal Immunol. 2020; Jan. 13(1):86–95.
Article
58. Huber C, Odermatt A, Hagmann B, Dahinden CA, Fux M. In human basophils, IL-3 selectively induces RANKL expression that is modulated by IgER-dependent and IgER-independent stimuli. Allergy. 2014; Nov. 69(11):1498–505.
Article
59. Huang Z, Hajjij A, Li G, Nayak JV, Zhou B, Hwang PH. Clinical predictors of neo-osteogenesis in patients with chronic rhinosinusitis. Int Forum Allergy Rhinol. 2015; Apr. 5(4):303–9.
Article
60. Karempelis P, Karp E, Rubin N, Hunter R, Dunitz J, Boyer H. Risk factors for neo-osteogenesis in cystic fibrosis and non-cystic fibrosis chronic rhinosinusitis. Int Forum Allergy Rhinol. 2020; Apr. 10(4):505–10.
Article
61. Dong D, Yulin Z, Xiao W, Hongyan Z, Jia L, Yan X, et al. Correlation between bacterial biofilms and osteitis in patients with chronic rhinosinusitis. Laryngoscope. 2014; May. 124(5):1071–7.
Article
62. Zhao YC, Wormald PJ. Biofilm and osteitis in refractory chronic rhinosinusitis. Otolaryngol Clin North Am. 2017; Feb. 50(1):49–60.
Article
63. Braga AA, Valera FC, Faria FM, Rossato M, Murashima AA, Fantucci MZ, et al. An experimental model of eosinophilic chronic rhinosinusitis induced by bacterial toxins in rabbits. Am J Rhinol Allergy. 2019; Nov. 33(6):737–50.
Article
64. Cho DY, Mackey C, Van Der Pol WJ, Skinner D, Morrow CD, Schoeb TR, et al. Sinus microanatomy and microbiota in a rabbit model of rhinosinusitis. Front Cell Infect Microbiol. 2018; Jan. 7:540.
Article
65. Shin HW. Animal models in CRS and pathophysiologic insights gained: a systematic review. Laryngoscope Investig Otolaryngol. 2016; Aug. 1(5):116–23.
Article
66. Perloff JR, Gannon FH, Bolger WE, Montone KT, Orlandi R, Kennedy DW. Bone involvement in sinusitis: an apparent pathway for the spread of disease. Laryngoscope. 2000; Dec. 110(12):2095–9.
Article
67. Khalid AN, Hunt J, Perloff JR, Kennedy DW. The role of bone in chronic rhinosinusitis. Laryngoscope. 2002; Nov. 112(11):1951–7.
Article
68. Dong Y, Zhou B, Wang X, Huang Z, Wang M, Li Y, et al. Computed tomography and histopathological evaluation of osteitis in rabbit models with rhinosinusitis. Acta Otolaryngol. 2017; May. 137(5):534–40.
Article
69. Khalmuratova R, Lee M, Kim DW, Park JW, Shin HW. Induction of nasal polyps using house dust mite and Staphylococcal enterotoxin B in C57BL/6 mice. Allergol Immunopathol (Madr). 2016; Jan-Feb. 44(1):66–75.
Article
70. Kim DW, Khalmuratova R, Hur DG, Jeon SY, Kim SW, Shin HW, et al. Staphylococcus aureus enterotoxin B contributes to induction of nasal polypoid lesions in an allergic rhinosinusitis murine model. Am J Rhinol Allergy. 2011; Nov-Dec. 25(6):e255–61.
Article
71. Wang S, Zhang H, Xi Z, Huang J, Nie J, Zhou B, et al. Establishment of a mouse model of lipopolysaccharide-induced neutrophilic nasal polyps. Exp Ther Med. 2017; Dec. 14(6):5275–82.
Article
72. Lee M, Kim DW, Yoon H, So D, Khalmuratova R, Rhee CS, et al. Sirtuin 1 attenuates nasal polypogenesis by suppressing epithelial-tomesenchymal transition. J Allergy Clin Immunol. 2016; Jan. 137(1):87–98.
Article
73. Lee M, Park CG, Huh BK, Kim SN, Lee SH, Khalmuratova R, et al. Sinonasal delivery of resveratrol via mucoadhesive nanostructured microparticles in a nasal polyp mouse model. Sci Rep. 2017; Jan. 7:40249.
Article
74. Kim SW, Kim JH, Jung MH, Hur DG, Lee HK, Jeon SY, et al. Periostin may play a protective role in the development of eosinophilic chronic rhinosinusitis with nasal polyps in a mouse model. Laryngoscope. 2013; May. 123(5):1075–81.
Article
75. Khalmuratova R, Lee M, Mo JH, Jung Y, Park JW, Shin HW. Wogonin attenuates nasal polyp formation by inducing eosinophil apoptosis through HIF-1α and survivin suppression. Sci Rep. 2018; Apr. 8(1):6201.
Article
76. Vandamme TF. Rodent models for human diseases. Eur J Pharmacol. 2015; Jul. 759:84–9.
Article
77. Wang Z, Chang L, Huang J, Huang Z, Li X, Chen X, et al. Histological and computed tomographic characteristics of the sinonasal structure of BALB/c mice. Anat Histol Embryol. 2020; Mar. 49(2):222–6.
Article
78. Kim SW, Kim DW, Khalmuratova R, Kim JH, Jung MH, Chang DY, et al. Resveratrol prevents development of eosinophilic rhinosinusitis with nasal polyps in a mouse model. Allergy. 2013; Jul. 68(7):862–9.
Article
79. Kim Y, Hwang S, Khalmuratova R, Kang S, Lee M, Song Y, et al. α-Helical cell-penetrating peptide-mediated nasal delivery of resveratrol for inhibition of epithelial-to-mesenchymal transition. J Control Release. 2020; Jan. 317:181–94.
Article
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