Osteoprotegerin expression and sensitivity in otosclerosis with different histological activity

Abstract

Otosclerosis is a complex bone dystrophy of the human otic capsule leading to conductive and sensorineural hearing loss. Since otosclerosis may, at least in part, be considered as an autoimmune-inflammatory disease, disturbed balance of TNF-alpha and osteoprotegerin (OPG) expression has been implicated in the pathological bone remodeling. It has been supposed that active otosclerosis is characterized by decreased or missing local OPG production with invariable OPG sensitivity of the otosclerotic foci. Ankylotic stapes footplates (n = 41) removed by stapedectomy were processed to histological examination, OPG-specific RT-PCR, tissue culturing and alkaline-phosphatase (AP) activity assessment, respectively. OPG concentration of serum specimens (n = 41) was measured by ELISA. Cortical bone fragments harvested from the external ear canal were used as negative controls of otosclerosis. Among 41 ankylotic stapes footplates, 22 active and 19 inactive otosclerosis cases were histologically diagnosed. OPG expression was significantly lower (p < 0.001) in active otosclerosis compared to inactive cases. Osteoclast cultures originated from active otosclerotic foci showed a considerable susceptibility against external OPG dosage, which resulted in a significant decrease of AP activity (p < 0.001). In contrast, OPG serum levels were in the normal range (5-100 ng/ml) indicating a non-systemic bone resorption. In conclusion, secondary decreased local OPG production might play an important role in the pathogenesis of otosclerotic bone remodeling disorder. As to previous and current results, decreased OPG sensitivity of lesion-forming cells should be excluded. These observations may indicate the potential role of recombinant OPG treatment in early stages of otosclerosis.

Genetic Association and Altered Gene Expression of Osteoprotegerin in Otosclerosis Patients

“…OPG, RANK, and RANKL mRNA was detected with 100% effectiveness in the specimens from cadavers and incus bones applied as negative controls for OTSC. The result of our finding is in accordance with the previous report which detected the OPG mRNA expression in all the cortical bone fragments applied as negative controls for OTSC (Karosi et al, 2011). Based on the established role of OPG as a powerful inhibitor of bone remodeling, our finding indicates that detectable OPG expression in all the normal tissue may be an important factor for normal bone remodeling in the otic capsule.…”

“…Gene expression profiling of disease tissue compared to controls has been suggested as a method to investigate the genetic basis of complex disorders (Xiong et al, 2012). Some of the studies have reported reduced or missing OPG expression in the otosclerotic tissue (Karosi et al, 2011;Potocka-Baklazec et al, 2014) but the exact mechanism that controls the altered OPG expression in OTSC is unclear. In this study, we aimed to identify the genetic risk factors in the OPG gene and to evaluate their potential role in OTSC development.…”

Loss of osteoprotegerin expression in the inner ear causes degeneration of the cochlear nerve and sensorineural hearing loss

“…While conductive hearing loss in some OPG-related disorders can be attributed, at least in part, to abnormal function of middle-ear bones that transmit acoustic vibrations to the inner ear (Whyte et al, 2002; Daroszewska and Ralston., 2006), mechanisms of sensorineural hearing loss in these disorders are poorly understood (Bahmad and Merchant, 2007; Karosi et al, 2011). …”

The Putative Role of Measles Virus in the Pathogenesis of Otosclerosis

“…Diffusion of OPG from the perilymph into the surrounding bone is intensive. Probably, this is one of the reasons why the otic capsule is unique in its morphology and development [ 60 ].…”