Expression of TNF-α, OPG, IL-1β and the presence of the measles virus RNA in the stapes of the patients with otosclerosis

Abstract

Persistent measles virus infections play a crucial role in the pathomechanism of otosclerosis. The study was undertaken to investigate the role of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and osteoprotegerin (OPG) in otosclerotic bone remodeling and to assess the relation of TNF-α, OPG and IL-1β expression levels in otosclerotic stape footplates to the occurrence of measles virus infection. 61 patients with otosclerosis were treated surgically. Thirty-one stapes obtained from cadavers of people, who had died from a sudden cause were used as a control group. The presence of measles virus RNA and the expression levels of TNF-α, IL-1β and OPG in otosclerotic foci were assessed using one-step RT-PCR. The presence of measles virus RNA was noted in 80.3 % of otosclerotic stapes (49 out of 61) and 9.7 % of normal tissues (3 out of 31). Transcript of TNF-α, IL-1β and OPG was detected in 40, 46 and 18 virus-positive stapes, respectively. The transcript level of TNF-α and IL-1β was significantly higher in otosclerotic tissues comparing to normal tissue. The OPG expression level was significantly lower in otosclerotic tissues comparing to controls. The presence of measles virus RNA in the stapes may indicate its role in the pathogenesis of otosclerosis. The presence of TNF-α and IL-1β mRNA in the virus-positive stapes could be the result of viral antigen stimulation and may be a marker of inflammation the otosclerotic focus. The lack of OPG mRNA and the presence of TNF-α and IL-1β mRNA in the majority of otosclerotic tissues reflect the bone remodeling process occurring in the stapes.

Genetic Association and Altered Gene Expression of Osteoprotegerin in Otosclerosis Patients

“…Previous studies have suggested that decreased or missing OPG expression in OTSC tissues can be a consequence of measles virus induced inflammatory reaction which leads to increased TNF-α and IL-1β production. The increased TNF-α and IL-1β and reduced OPG levels led to an antiapoptotic effect on osteoclasts which prolonged osteoclast life and abnormal bone remodeling in the otic capsule during OTSC (Karosi et al, 2006;Potocka-Baklazec et al, 2014). Bone remodeling, however is predominantly mediated by the OPG, RANK, and RANKL system but induced by factors such as mechanical stimuli, hormones, and cytokines (Hofbauer & Heufelder, 2001).…”

“…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.…”

Immune-Mediated Control of a Dormant Neurotropic RNA Virus Infection

“…For example, a positive MRZ reaction (intrathecal antibody directed against 2 of 3 viruses: MV, rubella virus, and varicella-zoster virus) is considered by some to be a prognostic indicator of MS, though this test is not in widespread clinical use. Further, persistent MV infection has been speculated as a causative agent of otosclerosis (localized bone displacement resulting in hearing loss) (38)(39)(40), suggesting again that an infection acquired earlier in life can contribute to diseases that are not typically attributed a viral etiology. Finally, a link has been proposed between cytomegalovirus (CMV) and glioblastoma, as anti-CMV treatments led to a reduction in glioblastoma tumor burden (41).…”

Can BRCA Mutation be a Risk Factor for Otosclerosis?

“…Additionally, OPG knockout mice have a progressive and severe hearing loss compared to controls, as determined by ABR and DPOAE tests (7). Studies have also demonstrated that OPG levels were low in patients with otosclerosis at both the tissue and gene level (18,19). In a histopathological study conducted on 41 patients, OPG levels observed in tissue cultures were lower in patients with active otosclerosis compared to those with inactive otosclerosis (20).…”