Konstantina M Stankovic1, Michael J McKenna. 1. Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114-3096, USA.
Abstract
PURPOSE OF REVIEW: The aim of this article is to summarize and put into historical perspective current advances in research in otosclerosis, a disorder of the human temporal bone with a hereditary predisposition that is among the most common causes of acquired hearing loss. RECENT FINDINGS: Genetic studies have revealed that otosclerosis is heterogeneous, with evidence for defects in at least seven genes associated with six distinct chromosomal loci. Measurements of high levels of osteoprotegerin expression in the normal otic capsule and soft tissues of the cochlea provide the first molecular insight as to why the normal otic capsule remodels minimally, if at all. Osteoprotegerin knockout mice provide the best available animal model to date to study abnormal otic capsule remodeling that closely resembles otosclerosis. There is mounting evidence that the measles virus plays an important role in pathogenesis of otosclerosis although the mechanisms by which the virus results in otosclerosis remain unknown. Quantitative measures of angiogenesis can reliably distinguish between clinical and histological otosclerosis. Advances in the emerging field of osteoimmunology will likely impact and benefit from the research in otosclerosis. SUMMARY: Insights into molecular mechanisms that inhibit extensive remodeling in the normal otic capsule, and understanding of how these mechanisms are dysregulated in otosclerosis will allow future design of rational treatment strategies for otosclerosis.
PURPOSE OF REVIEW: The aim of this article is to summarize and put into historical perspective current advances in research in otosclerosis, a disorder of the human temporal bone with a hereditary predisposition that is among the most common causes of acquired hearing loss. RECENT FINDINGS: Genetic studies have revealed that otosclerosis is heterogeneous, with evidence for defects in at least seven genes associated with six distinct chromosomal loci. Measurements of high levels of osteoprotegerin expression in the normal otic capsule and soft tissues of the cochlea provide the first molecular insight as to why the normal otic capsule remodels minimally, if at all. Osteoprotegerin knockout mice provide the best available animal model to date to study abnormal otic capsule remodeling that closely resembles otosclerosis. There is mounting evidence that the measles virus plays an important role in pathogenesis of otosclerosis although the mechanisms by which the virus results in otosclerosis remain unknown. Quantitative measures of angiogenesis can reliably distinguish between clinical and histological otosclerosis. Advances in the emerging field of osteoimmunology will likely impact and benefit from the research in otosclerosis. SUMMARY: Insights into molecular mechanisms that inhibit extensive remodeling in the normal otic capsule, and understanding of how these mechanisms are dysregulated in otosclerosis will allow future design of rational treatment strategies for otosclerosis.
Authors: Tamás Karosi; Péter Csomor; Anita Szalmás; József Kónya; Mihály Petkó; István Sziklai Journal: Eur Arch Otorhinolaryngol Date: 2010-10-21 Impact factor: 2.503