Auditory ossicle abnormalities and hearing loss in the toothless (osteopetrotic) mutation in the rat and their improvement after treatment with colony-stimulating factor-1
Auditory ossicle abnormalities and hearing loss in the toothless (osteopetrotic) mutation in the rat and their improvement after treatment with colony-stimulating factor-1
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DOI：
10.1359/jbmr.1999.14.3.415
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发表时间：
1999-03-01
影响因子：
6.2
通讯作者：
Marks, SC
中科院分区：
文献类型：
--
作者：
Aharinejad, S;Grossschmidt, K;Marks, SC
石骨症描述了一组具有异质性病因和不同严重程度的骨骼代谢疾病，其产生骨骼质量的普遍积累，这是骨吸收减少的结果;在包括人类在内的多种物种中遗传，最严重的形式是致命的。常见的特征是病因有争议的进行性失明和耳聋，对此没有普遍有效的治疗方法。我们研究了无牙（tl）大鼠的听觉反应性、听小骨定量组织形态学和颞骨血管，无牙大鼠是一种致死性骨硬化突变，具有破骨细胞少、骨转换极低和中轴骨骼血管生成受限的特点。与正常同窝出生的小鼠相比，3周龄的突变体表现出明显降低的听觉反应性，由于镫骨的形式和组织成分异常而导致的听力损失，以及颞骨血管床中的小毛细血管发芽。用集落刺激因子1（CSF-1）治疗突变体，已知可大大减少中轴骨骼的硬化，显着改善听力，镫骨形式和组织组成，以及颞骨中的血管生成。在正常大鼠中，镫骨由89.3%的骨、9.1%的矿化软骨和0.8%的孔隙组成。在骨硬化大鼠中，镫骨由48.3%的骨、35.9%的矿化软骨和15.9%的孔隙组成，而CSF-1治疗后，骨含量增加至55.2%，软骨减少至21.7%，孔隙增加至23.0%。这是第一次证明骨硬化动物突变中的听觉异常，并表明在用CSF-1治疗后，tl大鼠中的听力损失可以显著改善。
Osteopetrosis describes a group of skeletal metabolic diseases of heterogeneous etiology and varied severity that produces a generalized accumulation df skeletal mass, the result of reduced bone resorption; Inherited in a variety of species including humans, the most severe forms are lethal. Among common features are progressive blindness and deafness of controversial etiologies for which there are no universally effective treatments. We have studied the auditory responsiveness and auditory ossicle quantitative histomorphology and temporal bone vasculature in the toothless (tl) rat, a lethal osteopetrotic mutation with few osteoclasts, very low bone turnover, and limited angiogenesis in the axial skeleton. Compared with normal littermates, 3-week-old mutants showed significantly reduced auditory responsiveness, a hearing loss due to abnormalities in both form and tissue composition of the stapes, and little capillary sprouting in the vascular bed of the temporal bone. Treatment of mutants with colony-stimulating factor 1 (CSF-1), known to greatly reduce sclerosis in the axial skeleton, significantly improved hearing, stapedial form and tissue composition, and angiogenesis in the temporal bone. In normal rats, the stapes consisted of 89.3% bone, 9.1% mineralized cartilage, and 0.8% porosity. In osteopetrotic rats, the stapes consisted of 48.3% bone, 35.9% mineralized cartilage, and 15.9% porosity, while after CSF-1 treatment, the bone content increased to 55.2%, cartilage was decreased to 21.7%, and porosity increased to 23.0%, respectively. This is the first demonstration of an auditory abnormality in an osteopetrotic animal mutation and shows that the hearing loss in tl rats can be significantly improved following treatment with CSF-1.