Loss of osteoprotegerin expression in the inner ear causes degeneration of the cochlear nerve and sensorineural hearing loss
Copyright policy )Loss of osteoprotegerin expression in the inner ear causes degeneration of the cochlear nerve and sensorineural hearing loss
Osteoprotegerin (OPG) is a key regulator of bone remodeling. Mutations and variations in the OPG gene cause many human diseases that are characterized by not only skeletal abnormalities but also poorly understood hearing loss: Paget's disease, osteoporosis, and celiac disease. To gain insight into the mechanisms of hearing loss in OPG deficiency, we studied OPG knockout (Opg(-/-)) mice. We show that they develop sensorineural hearing loss, in addition to conductive hearing loss due to abnormal middle-ear bones. OPG deficiency caused demyelination and degeneration of the cochlear nerve in vivo. It also activated ERK, sensitized spiral ganglion cells (SGC) to apoptosis, and inhibited proliferation and survival of cochlear stem cells in vitro, which could be rescued by treatment with exogenous OPG, an ERK inhibitor, or bisphosphonate. Our results demonstrate a novel role for OPG in the regulation of SGC survival, and suggest a mechanism for sensorineural hearing loss in OPG deficiency.
- Harvard University United States
- Massachusetts Eye and Ear Infirmary United States
Auditory stem cell, Plastic Embedding, Cell Survival, Hearing Loss, Sensorineural, Neurosciences. Biological psychiatry. Neuropsychiatry, Apoptosis, Enzyme-Linked Immunosorbent Assay, Mice, Neural Stem Cells, Cochlear neurons, Animals, Cochlear Nerve, Cells, Cultured, In Situ Hybridization, Mice, Knockout, Paraffin Embedding, Osteoprotegerin, Spiral ganglion cells, Immunohistochemistry, Sensorineural hearing loss, Mice, Inbred C57BL, Oxidative Stress, Phenotype, Ear, Inner, Nerve Degeneration, RC321-571
Auditory stem cell, Plastic Embedding, Cell Survival, Hearing Loss, Sensorineural, Neurosciences. Biological psychiatry. Neuropsychiatry, Apoptosis, Enzyme-Linked Immunosorbent Assay, Mice, Neural Stem Cells, Cochlear neurons, Animals, Cochlear Nerve, Cells, Cultured, In Situ Hybridization, Mice, Knockout, Paraffin Embedding, Osteoprotegerin, Spiral ganglion cells, Immunohistochemistry, Sensorineural hearing loss, Mice, Inbred C57BL, Oxidative Stress, Phenotype, Ear, Inner, Nerve Degeneration, RC321-571
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