Bisphosphonate Therapy Ameliorates Hearing Loss in Mice Lacking Osteoprotegerin
Bisphosphonate Therapy Ameliorates Hearing Loss in Mice Lacking Osteoprotegerin
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DOI：
10.1359/jbmr.080812
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发表时间：
2009-01-01
影响因子：
6.2
通讯作者：
Matsuo, Koichi
中科院分区：
文献类型：
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作者：
Kanzaki, Sho;Takada, Yasunari;Matsuo, Koichi
三个听小骨，包括锤骨、砧骨和镫骨，在中间从鼓膜到内耳传导声音。Opg（-/-）小鼠的听小骨被破骨细胞大量吸收。其缺乏骨保护素（OPG），一种破骨细胞生成细胞因子gRANKL的可溶性诱饵受体。Opg（-/-）小鼠表现出进行性听力损失，并且是幼年佩吉特病的模型。然而，抗吸收治疗对Opg（-/-）小鼠听小骨和听力功能的影响尚不清楚。我们用双膦酸利塞膦酸钠腹腔注射Opg（-/-）小鼠5 d/wk，共9 wk。听小骨的形态进行了检查，显微镜，X线片，和组织学。采用听性脑干反应（ABR）检测听功能。对照Opg（-/-）小鼠表现出所有三个听小骨和胫骨变薄。相反，利塞膦酸钠治疗显著抑制Opg（-/-）小鼠听小骨和长骨的骨丢失。治疗后，镫骨和耳囊之间连接处的骨融合减少。ABR检测结果显示，利塞膦酸钠能显著改善Opg（-/-）小鼠的听力。这些数据表明，听力损失的病理特点是过度吸收的听小骨可以防止双膦酸盐。
Three auditory ossicles including the malleus, incus, and stapes conduct sound in the middle eat from the tympanic membrane to the inner ear. Auditory ossicles are massively resorbed by osteoclasts in Opg(-/-) mice. which lack osteoprotegerin (OPG), a soluble decoy receptor for the osteoclastogenic cytokine g RANKL. Opg(-/-) mice exhibit progressive hearing loss and are a model for juvenile Paget's disease. However, effects of antiresorptive treatment on auditory ossicles and on hearing function in Opg(-/-) mice are unknown. We intraperitoneally injected Opg(-/-) mice with bisphosphonate risedronate 5 d/wk for 9 wk. Morphology of auditory ossicles was examined microscopically, radiographically, and histologically. Hearing function was monitored by measuring the auditory brain stem response (ABR). Control Opg(-/-) mice exhibited thinning of all three ossicles and tibia. In contrast, risedronate treatment significantly inhibited bone loss in auditory ossicles as well as in long bones of Opg(-/-) mice. Bony fusion of the junction between the stapes and the otic capsule was reduced after treatment. Moreover, ABR measurement showed that hearing in Opg(-/-) mice was significantly improved by risedronate treatment. These data suggest that hearing loss in pathologies characterized by excessive resorption of the auditory ossicles may be prevented by bisphosphonates.