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Impaired vibration of auditory ossicles in osteopetrotic mice.

ABSTRACT: In the middle ear, a chain of three tiny bones (ie, malleus, incus, and stapes) vibrates to transmit sound from the tympanic membrane to the inner ear. Little is known about whether and how bone-resorbing osteoclasts play a role in the vibration of auditory ossicles. We analyzed hearing function and morphological features of auditory ossicles in osteopetrotic mice, which lack osteoclasts because of the deficiency of either cytokine RANKL or transcription factor c-Fos. The auditory brainstem response showed that mice of both genotypes experienced hearing loss, and laser Doppler vibrometry revealed that the malleus behind the tympanic membrane failed to vibrate. Histological analysis and X-ray tomographic microscopy using synchrotron radiation showed that auditory ossicles in osteopetrotic mice were thicker and more cartilaginous than those in control mice. Most interestingly, the malleal processus brevis touched the medial wall of the tympanic cavity in osteopetrotic mice, which was also the case for c-Src kinase-deficient mice (with normal numbers of nonresorbing osteoclasts). Osteopetrotic mice showed a smaller volume of the tympanic cavity but had larger auditory ossicles compared with controls. These data suggest that osteoclastic bone resorption is required for thinning of auditory ossicles and enlargement of the tympanic cavity so that auditory ossicles vibrate freely.

SUBMITTER: Kanzaki S

PROVIDER: S-EPMC3070593 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Impaired vibration of auditory ossicles in osteopetrotic mice.

Kanzaki Sho S Takada Yasunari Y Niida Shumpei S Takeda Yoshihiro Y Udagawa Nobuyuki N Ogawa Kaoru K Nango Nobuhito N Momose Atsushi A Matsuo Koichi K

The American journal of pathology 20110301 3

In the middle ear, a chain of three tiny bones (ie, malleus, incus, and stapes) vibrates to transmit sound from the tympanic membrane to the inner ear. Little is known about whether and how bone-resorbing osteoclasts play a role in the vibration of auditory ossicles. We analyzed hearing function and morphological features of auditory ossicles in osteopetrotic mice, which lack osteoclasts because of the deficiency of either cytokine RANKL or transcription factor c-Fos. The auditory brainstem resp ...[more]

PMID: 21356377

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Project description:SignificanceMeasurements of auditory ossicles displacement are commonly carried out by means of laser-Doppler vibrometry (LDV), which is considered to be a gold standard. The limitation of the LDV method, especially for in vivo measurements, is the necessity to expose an object in a straight line to a laser beam operating from a distance. An alternative to this approach is the use of a handheld laser-fiber vibrometry probe (HLFVP) with a curved tip.AimWe evaluate the feasibility of an HLFVP with a curved tip for measuring sound-induced displacement of the auditory ossicles.ApproachA handheld vibrometer probe guiding the laser beam with a fiber-optic cable was used for displacement measurements of the incus body and the posterior crus of the stapes. Tonal stimuli at frequencies of 0.5, 1, 2, and 4 kHz were presented by means of an insert earphone positioned in the outer ear canal. The probe was fixed at the measurement site using a tripod or hand-held by one of the two surgeons.ResultsThe measurements were carried out on six fresh temporal bones. Multivariate analysis of variance showed statistically significant differences for stimulus frequency (F3,143 = 29.37, p < 0.001, and η2 = 0.35), bone (F5,143 = 4.61, p = 0.001, and η2 = 0.01), and measurement site (F1,143 = 4.74, p = 0.03, and η2 = 0.02) in the absence of statistically significant differences for the probe fixation method (F2,143 = 0.15, p = 0.862, and η2 = 0.001). Standard deviations of the means were 6.9, 2.6, 1.9, and 0.6 nm / Pa for frequency, bone, site, and fixation, respectively. Ear transfer functions were found to be consistent with literature data.ConclusionsThe feasibility of applying HLFVP to measure the displacement of auditory ossicles has been confirmed. HLFVP offers the possibility of carrying out measurements at various angles; however, this needs to be standardized taking into account anatomical limitations and surgical convenience.

Project description:Background and Purpose: Auditory processing disorders (APD), tinnitus and hearing loss (HL) are typical issues reported by patients in audiologic clinics. These auditory impairments can be concomitant or mutually excluding. APD are not necessarily accompanied by significant HL, whereas many adults exhibit peripheral HL and typical cognitive deficits often associated with APD. Since HL, tinnitus and APD affects to several parts of the ascending auditory pathway from the periphery to the auditory cortex, there could be some interrelationship between them. For instance, tinnitus has been reported to degrade the auditory localization capacity. Tinnitus is believed to be triggered by deafferentation of normal peripheral input to the central auditory system. This peripheral deficit can be accompanied by HL or not, since a type of permanent cochlear damage (thus deafferentation) without an elevation of hearing thresholds might persist. Therefore, a combined study of APD, tinnitus and HL on the same cohort of patients can be audiologically relevant and worthy. Methods: Statistical analysis is applied to a cohort of 305 patients attending an audiology clinic in Madrid (Spain). This group of patients is first categorized in four subgroups, namely, HLTG (with tinnitus and HL), NHLTG (with tinnitus and without HL), HLNTG (with HL but no tinnitus), and NHLNTG (neither tinnitus nor HL). The statistical variables include Age, Average Auditory Threshold (ATT), for assessing HL, Tinnitus Handicap Inventory (THI), for measuring tinnitus, and a new 25-item Auditory Behavior Questionnaire (ABQ), for scoring APD. Factor analysis is applied to arrange these items into 4 subscales. The internal consistency reliability of this ABQ is confirmed by calculating Cronbach's coefficients α. The test-retest reliability is assessed by the intraclass correlation coefficients, ICC. Statistical techniques applied to the data set include descriptive analysis of variables and Spearman rank correlations (ρ) between them. Results: Overall reliability of ABQ is confirmed by an α value of 0.89 and by an ICC of 0.91. Regarding the internal consistency reliability, the four subscales prove a fairly good consistency with α coefficients above 0.7. Average values of statistical variables show significantly lower age of patients with tinnitus and no HL, which can provide a cue of noise overexposure of this segment of population. These younger patients show also decreased ABQ and similar THI in comparison with patients in the other subgroups. A strong correlation (ρ = 0.63) was found between AAT and Age for the HLNTG subgroup. For the HLTG subgroup, a moderate correlation (ρ = 0.44) was found between ABQ and THI. Conclusion: The utilized questionnaire (ABQ), together with AAT and THI, can help to study comorbid hearing impairments in patients regularly attending an audiological clinic.

Dataset Information

Impaired vibration of auditory ossicles in osteopetrotic mice.

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Impaired vibration of auditory ossicles in osteopetrotic mice.

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