Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-28T16:30:32.007Z Has data issue: false hasContentIssue false

Possible role of Dickkopf-1 protein in the pathogenesis of tympanosclerosis in a rat model

Published online by Cambridge University Press:  15 August 2017

Y Zhang
Affiliation:
Department of Otolaryngology – Head and Neck Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
S Wang
Affiliation:
Department of Otolaryngology – Head and Neck Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
Y Zheng
Affiliation:
Department of Otolaryngology – Head and Neck Surgery, Central Hospital of Wuhan, Huazhong University of Science and Technology, Wuhan, China
A Liu*
Affiliation:
Department of Otolaryngology – Head and Neck Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
*
Address for correspondence: Dr Aiguo Liu, Department of Otolaryngology – Head and Neck Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China E-mail: aiguoliu309@163.com

Abstract

Objectives:

This study aimed to investigate the expression of DKK1 protein in an experimental model of tympanosclerosis and its possible role in the pathogenesis of this disorder.

Methods:

Forty Sprague Dawley rats were included in the study: 20 in the control group (which received no treatment) and 20 in the experimental group (which received an incision to induce tympanosclerosis). Otomicroscopy was performed to observe the development of myringosclerosis. Haematoxylin and eosin staining was performed to observe the morphological changes. Western blot analysis and immunohistochemistry were performed to assess the expression of DKK1 protein.

Results:

At day 15, sclerotic lesions were observed in 70 per cent of the tympanic membranes. Inflammatory infiltration and hyaline degeneration markedly appeared in the tympanic membranes and middle-ear mucosa. DKK1 protein was mainly distributed in the cytoplasm of epithelial cells, which were widely distributed in the tympanic membranes and middle-ear mucosa. The expression of DKK1 protein was significantly decreased in the calcified experimental ears.

Conclusion:

DKK1 protein is involved in the pathogenesis of tympanosclerosis by regulating the Wnt/β-catenin signalling pathway.

Type
Main Articles
Copyright
Copyright © JLO (1984) Limited 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1 Wielinga, EW, Kerr, AG. Tympanosclerosis. Clin Otolaryngol Allied Sci 1993;18:341–9CrossRefGoogle ScholarPubMed
2 Asiri, S, Hasham, A, al Anazy, F, Zakzouk, S, Banjar, A. Tympanosclerosis: review of literature and incidence among patients with middle-ear infection. J Laryngol Otol 1999;113:1076–80Google Scholar
3 Mattsson, C, Magnuson, K, Hellstrom, S. Myringosclerosis caused by increased oxygen concentration in traumatized tympanic membranes. Experimental study. Ann Otol Rhinol Laryngol 1995;104:625–32CrossRefGoogle ScholarPubMed
4 Kinis, V, Ozbay, M, Alabalik, U, Gul, A, Yilmaz, B, Ozkurt, FE et al. Effect of caffeic acid phenethyl ester on myringosclerosis development in the tympanic membrane of rat. Eur Arch Otorhinolaryngol 2015;272:2934 Google Scholar
5 Russell, JD, Giles, JJ. Tympanosclerosis in the rat tympanic membrane: an experimental study. Laryngoscope 2002;112:1663–6Google Scholar
6 Forseni, M, Eriksson, A, Bagger-Sjoback, D, Nilsson, J, Hultcrantz, M. Development of tympanosclerosis: can predicting factors be identified? Am J Otol 1997;18:298303 Google Scholar
7 Koc, A, Uneri, C. Genetic predisposition for tympanosclerotic degeneration. Eur Arch Otorhinolaryngol 2002;259:180–3Google Scholar
8 Ferlito, A. Histopathogenesis of tympanosclerosis. J Laryngol Otol 1979;93:2537 CrossRefGoogle ScholarPubMed
9 Makishima, K, Toriya, Y, Inoue, S, Nakashima, T, Igarashi, Y. Clinicopathologic studies in tympanosclerosis. Am J Otol 1982;3:260–5Google ScholarPubMed
10 Tos, M, Stangerup, SE. Hearing loss in tympanosclerosis caused by grommets. Arch Otolaryngol Head Neck Surg 1989;115:931–5Google Scholar
11 Olsson, M, Dalsgaard, CJ, Haegerstrand, A, Rosenqvist, M, Ryden, L, Nilsson, J. Accumulation of T lymphocytes and expression of interleukin-2 receptors in nonrheumatic stenotic aortic valves. J Am Coll Cardiol 1994;23:1162–70Google Scholar
12 Mann, W, Beck, C, Schaefer, HE. The significance of calcium antagonists in rat experimental tympanosclerosis. Arch Otorhinolaryngol 1987;243:382–6CrossRefGoogle ScholarPubMed
13 Haynes, KR, Pettit, AR, Duan, R, Tseng, HW, Glant, TT, Brown, MA et al. Excessive bone formation in a mouse model of ankylosing spondylitis is associated with decreases in Wnt pathway inhibitors. Arthritis Res Ther 2012;14:R253 CrossRefGoogle Scholar
14 Rossini, M, Gatti, D, Adami, S. Involvement of WNT/beta-catenin signaling in the treatment of osteoporosis. Calcif Tissue Int 2013;93:121–32Google Scholar
15 Walsh, NC, Gravallese, EM. Bone remodeling in rheumatic disease: a question of balance. Immunol Rev 2010;233:301–12Google Scholar
16 Huang, H, Wu, P, Cui, Y, Ge, R, Zhang, L. Expressions of OPG and RANKL in a rat model of tympanosclerosis [in Chinese]. Chinese Journal of Otology 2013;2:302–5Google Scholar
17 Boyce, BF, Xing, L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 2008;473:139–46Google Scholar
18 Belibasakis, GN, Bostanci, N. The RANKL-OPG system in clinical periodontology. J Clin Periodontol 2012;39:239–48Google Scholar
19 Glass, DA 2nd, Karsenty, G. Canonical Wnt signaling in osteoblasts is required for osteoclast differentiation. Ann N Y Acad Sci 2006;1068:117–30CrossRefGoogle ScholarPubMed
20 Glass, DA 2nd, Bialek, P, Ahn, JD, Starbuck, M, Patel, MS, Clevers, H et al. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 2005;8:751–64CrossRefGoogle ScholarPubMed
21 Baron, R, Rawadi, G. Targeting the Wnt/beta-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology 2007;148:2635–43Google Scholar
22 Baron, R, Kneissel, M. WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med 2013;19:179–92Google Scholar
23 Fedi, P, Bafico, A, Nieto Soria, A, Burgess, WH, Miki, T, Bottaro, DP et al. Isolation and biochemical characterization of the human Dkk-1 homologue, a novel inhibitor of mammalian Wnt signaling. J Biol Chem 1999;274:19465–72Google Scholar
24 Kawano, Y, Kypta, R. Secreted antagonists of the Wnt signalling pathway. J Cell Sci 2003;116:2627–34Google Scholar
25 Sakalli, E, Baylancicek, S, Yuksel, M, Erdurak, SC, Dadas, B. Levels of reactive oxygen species in rat tympanic membranes after incisional versus radiofrequency myringotomy. Int J Pediatr Otorhinolaryngol 2013;77:792–5Google Scholar
26 Erdurak, SC, Coskun, BU, Sakalli, E, Tansuker, HD, Turan, F, Kaya, D. Does the use of radiofrequency myringotomy for insertion of a ventilation tube reduce the incidence of myringosclerosis? Eur Arch Otorhinolaryngol 2014;271:459–62Google Scholar
27 Mattsson, C, Magnuson, K, Hellstrom, S. Myringotomy: a prerequisite for the development of myringosclerosis? Laryngoscope 1998;108:102–6CrossRefGoogle ScholarPubMed
28 Song, JJ, Kwon, SK, Cho, CG, Park, SW. The effect of caffeic acid phenethyl ester on the prevention of experimentally induced myringosclerosis. Int J Pediatr Otorhinolaryngol 2007;71:1287–91Google Scholar
29 NaderPour, M, Moghaddam, YJ, Peirovifar, A, Mollajavadi, R, Abbasi, MM, Mohajeri, D. Microscopic comparison of topical use of Mitomycin C and Fluorouracil on cold knife myringotomy. Int J Pediatr Otorhinolaryngol 2012;76:913 Google Scholar
30 Dogan, E, Erdag, TK, Sarioglu, S, Ecevit, MC, Ikiz, AO, Guneri, EA. The preventive effect of N-nitro L-arginine methyl ester in experimentally induced myringosclerosis. Int J Pediatr Otorhinolaryngol 2011;75:1035–9Google Scholar
31 Mattsson, C, Hellstrom, S. Inhibition of the development of myringosclerosis by local administration of fenspiride, an anti-inflammatory drug. Eur Arch Otorhinolaryngol 1997;254:425–9CrossRefGoogle ScholarPubMed
32 Li, J, Sarosi, I, Cattley, RC, Pretorius, J, Asuncion, F, Grisanti, M et al. Dkk1-mediated inhibition of Wnt signaling in bone results in osteopenia. Bone 2006;39:754–66Google Scholar
33 Ueland, T, Otterdal, K, Lekva, T, Halvorsen, B, Gabrielsen, A, Sandberg, WJ et al. Dickkopf-1 enhances inflammatory interaction between platelets and endothelial cells and shows increased expression in atherosclerosis. Arterioscler Thromb Vasc Biol 2009;29:1228–34Google Scholar
34 Yamaguchi, Y, Passeron, T, Hoashi, T, Watabe, H, Rouzaud, F, Yasumoto, K et al. Dickkopf 1 (DKK1) regulates skin pigmentation and thickness by affecting Wnt/beta-catenin signaling in keratinocytes. FASEB J 2008;22:1009–20CrossRefGoogle ScholarPubMed