title: 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.
authors.affiliation: Department of Otolaryngology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Kanzaki
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Takada
authors.forename: Shumpei
authors.initials: S
authors.lastname: Niida
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takeda
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Udagawa
authors.forename: Kaoru
authors.initials: K
authors.lastname: Ogawa
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Nango
authors.forename: Atsushi
authors.initials: A
authors.lastname: Momose
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuo
mesh_terms: D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002356:Cartilage / Q000473:pathology; D019902:Chondrocytes / Q000473:pathology; D004429:Ear Ossicles / Q000000981:diagnostic imaging / Q000473:pathology*; D034381:Hearing Loss / Q000150:complications / Q000473:pathology; D008307:Malleus / Q000000981:diagnostic imaging / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D010022:Osteopetrosis / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000172:deficiency / Q000378:metabolism; D017356:Synchrotrons; D013701:Temporal Bone / Q000473:pathology; D014732:Vibration; D055114:X-Ray Microtomography; D019061:src-Family Kinases
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases