Resorption of auditory ossicles and hearing loss in mice lacking osteoprotegerin.
Bones conduct sound in the middle ear. The three ossicles-the malleus, incus, and stapes-form a chain that transmits vibrations from the tympanic membrane to the oval window of the inner ear. Little is known about bone remodeling events in these ossicles and about potential effects of osteoporosis on hearing loss. Osteoclastic bone resorption is enhanced in Opg(-/-) mice lacking osteoprotegerin, which is a soluble decoy receptor for the osteoclastogenic cytokine RANKL. We asked whether auditory ossicles are resorbed in Opg(-/-) mice, and whether these mice suffer from impaired auditory function. All three ossicles in Opg(-/-) mice showed thinning, especially at the malleal manubrium and incus body. Most notably, unlike in the case in wild-type mice, the junction between the stapes and the otic capsule was fixed in Opg(-/-) mice, and the stapedial footplate was thinner and broader. Radiological analyses revealed that malleal cortical thickness was positively correlated with tibial bone mineral density in Opg(-/-) and control littermate mice. Furthermore, progressive hearing loss was detected in Opg(-/-) mice starting at 6 to 15 weeks of age. These data suggest that osteoprotegerin plays a crucial role in hearing by protecting the auditory ossicles and otic capsule from osteoclastic bone resorption.
Department of Otolaryngology, School of Medicine, Keio University, 35 Shinanomachi, Tokyo 160-8582, Japan.
Sho
S
Kanzaki
Masako
M
Ito
Yasunari
Y
Takada
Kaoru
K
Ogawa
Koichi
K
Matsuo
D000161:Acoustic Stimulation; D000818:Animals; D001862:Bone Resorption / Q000235:genetics / Q000473:pathology*; D004429:Ear Ossicles / Q000000981:diagnostic imaging / Q000473:pathology*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000235:genetics / Q000502:physiology; D005260:Female; D006023:Glycoproteins / Q000235:genetics*; D034381:Hearing Loss / Q000235:genetics* / Q000503:physiopathology*; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053244:Osteoprotegerin; D011859:Radiography; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D013997:Time Factors
D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506031:Tnfrsf11b protein, mouse