![]() ![]() ![]() Mice lacking OPG show abnormal remodeling of the otic capsule and auditory ossicles induced by osteoclast hyperactivity ( Zehnder et al., 2005 Kanzaki et al., 2006). ![]() Osteoprotegerin (OPG) is a key regulator of bone homeostasis. Auditory brainstem and visual evoked potentials are both abnormal in CSF-1-deficient mice ( Michaelson et al., 1996). The osteopetrotic mutation toothless (tl) rat exhibits auditory ossicle abnormalities and hearing loss due to the truncated Csf1 gene (encoding colony-stimulating facter-1, CSF-1) and non-functional protein ( Aharinejad et al., 1999 Van Wesenbeeck et al., 2002). ![]() There are many animal models of osteosclerosis with hearing-related symptoms. These findings suggest that osteosclerosis-related genes are also involved in the formation and maintenance of normal hearing. Most cases of osteosclerosis are caused by genetic mutations, but a few cases still lack an accurate molecular diagnosis ( Sobacchi et al., 2013). Most deaf patients present with conductive deafness due to abnormalities of the auditory ossicles or temporal bone, while some present with sensorineural or mixed hearing loss ( Stocks et al., 1998 Dozier et al., 2005). Approximately 80% of patients with osteosclerosis develop hearing loss in childhood. In addition to skeletal lesions, patients with osteopetrosis are often also affected by neurological complications, notably hearing loss or visual impairment. Osteoclast-mediated bone resorption plays a vital role in bone homeostasis, and perturbation of this process can lead to profound alterations in bone mass that have clinical relevance. This leads to a marked increase in bone density due to defective bone resorption ( Del Fattore et al., 2008). Osteopetrosis is a rare bone disorder caused by the absence or dysfunction of osteoclasts. Bony remodeling disorders of the auditory ossicles and otic capsule are involved in the hearing loss caused by CDCC154 mutation. Our results indicate that mutation of the osteopetrosis-related gene CCDC154 can induce syndromic hereditary deafness in mice. Normal structure of the organ of Corti and no substantial hair cell or spiral ganglion neuron loss was observed in homozygous mutant mice. Pathological observation showed that abnormal bony remodeling of the otic capsule, characterized by increased vascularization and multiple cavitary lesions, was found in homozygous mutant mice. Homozygous mutant mice showed moderate to severe hearing loss, while heterozygous or wild-type (WT) littermates displayed normal hearing. In this study, we found that a spontaneous mutation of coiled-coil domain-containing 154 (CCDC154) gene, a new osteopetrosis-related gene, induced congenital deafness in mice. However, the etiology and pathogenesis of auditory damage still need to be explored. Hearing loss is one of the most common complications of osteopetrosis. Osteopetrosis is a rare inherited bone disease characterized by dysfunction of osteoclasts, causing impaired bone resorption and remodeling, which ultimately leads to increased bone mass and density. 2Department of Otolaryngology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.1Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Kai Xu 1† Xue Bai 1† Sen Chen 1† Le Xie 1 Yue Qiu 1 He Li 2* Yu Sun 1* ![]()
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