Eaton Peabody Laboratory and Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA 02114-3096, USA.
Hear Res. 2010 Jun 14;265(1-2):83-9. doi: 10.1016/j.heares.2010.02.006. Epub 2010 Feb 8.
Our long term goal is to understand the molecular pathology of otosclerosis and to develop better forms of therapy. Toward this goal, the current study focused on characterizing the molecular factors responsible for the unique biological features of the otic capsule: its minimal rate of remodeling, and lack of healing capacity when fractured. We compared expression levels of 62 genes involved in bone metabolism between the adult murine otic capsule and the tibia and parietal bones; the latter exemplify bones formed by endochondral and intramembranous ossification, respectively. Gene expression levels were measured using real-time quantitative RT-PCR and analyzed using tools of bioinformatics. Expression patterns of key genes were verified with in situ hybridization. The molecular profile of the otic capsule was distinctly different from that of the tibia and parietal bone. Genes found to be most characteristic of the otic capsule were: osteoprotegerin (opg), bone morphogenetic protein receptor 1b (bmpr1b) and bone morphogenetic protein 3 (bmp3). Expression levels were high for opg and bmpr1b, and minimal for bmp3 within the otic capsule. We concluded that opg and bmpr1b likely play important roles in inhibition of remodeling within the otic capsule.
我们的长期目标是了解耳硬化症的分子病理学,并开发更好的治疗方法。为了实现这一目标,本研究集中于描述负责耳壳独特生物学特征的分子因素:其重塑率低,骨折时缺乏愈合能力。我们比较了 62 个参与骨代谢的基因在成年鼠耳壳和胫骨及顶骨之间的表达水平;后者分别代表由软骨内骨化和膜内成骨形成的骨骼。使用实时定量 RT-PCR 测量基因表达水平,并使用生物信息学工具进行分析。用原位杂交验证关键基因的表达模式。耳壳的分子特征明显不同于胫骨和顶骨。被认为最能代表耳壳的基因有:护骨素(opg)、骨形态发生蛋白受体 1b(bmpr1b)和骨形态发生蛋白 3(bmp3)。opg 和 bmpr1b 在耳壳中的表达水平较高,而 bmp3 的表达水平较低。我们得出结论,opg 和 bmpr1b 可能在抑制耳壳内重塑中发挥重要作用。