Increased Activity of the Diastrophic Dysplasia Sulfate Transporter in Otosclerosis and Its Inhibition by Sodium Fluoride
Increased Activity of the Diastrophic Dysplasia Sulfate Transporter in Otosclerosis and Its Inhibition by Sodium Fluoride
复制标题
耳硬化症中破坏性发育不良硫酸盐转运蛋白活性的增加及其氟化钠的抑制作用
作者：
A. B. Grayeli;B. Escoubet;M. Bichara;N. Julien;C. Silve;G. Friedlander;O. Sterkers;E. Ferrary
本研究探讨了大鼠耳硬化骨中失调性硫酸盐发育不良转运蛋白（DTDST）的功能及氟化钠（NaF）对其的影响。背景：耳硬化是一种伴有骨转换增加的局部骨营养不良。DTDST与骨转换的调节有关。材料与方法对26例耳硬化症患者的镫骨和外耳道（EAC）细胞进行原代培养。在基础条件和NaF条件下定量测定硫酸盐吸收量。用福斯克林和维拉帕米研究了NaF信号通路。结果硫酸盐吸收的相对初始速率和表观Vmax值为：耳硬化镫骨> EAC >对照镫骨=对照EAC。耳硬化镫骨对硫酸盐的摄取与感觉神经性听力的丧失有关。四个亚组中DTDST mRNA （RNase保护试验）的数量没有差异。NaF（10−6M， 1小时）抑制耳硬化镫骨细胞和EAC细胞对硫酸盐的摄取，但对对照样品无抑制作用。结论无论DTDST活性的增加是耳硬化的原因还是结果，它似乎都是NaF治疗的特异性靶点。
Hypothesis This study investigates the function of the diastrophic dysplasia sulfate transporter (DTDST) in otosclerotic bone and the effect on it of sodium fluoride (NaF). Background Otosclerosis is a localized bone dystrophy with increased bone turnover. DTDST is implicated in the regulation of the bone turnover. Materials and Methods Primary cultures of cells were obtained from the stapes and external auditory canal (EAC) of 26 patients with otosclerosis and from nine control patients. Sulfate uptake was quantified under basal conditions and with NaF. The NaF signaling pathways were investigated using forskolin and verapamil. Results The relative initial rates of sulfate uptake and the apparent Vmax values were: otosclerotic stapes > EAC > control stapes = control EAC. The sulfate uptake by the otosclerotic stapes was correlated with the loss of sensorineural hearing. The amounts of DTDST mRNA (RNase protection assay) in the four subgroups did not differ. NaF (10−6M, 1 hr) inhibited sulfate uptake by the otosclerotic stapes and EAC cells but not by control samples. Conclusion The authors believe that whether the increased DTDST activity is a cause or an effect of otosclerosis, it appears to be a specific target for NaF treatment.
耳硬化症：全身性结缔组织疾病的局部表现？
影响因子：
2.5
作者：
Thalmann,I;Thallinger,G;Thalmann,R
通讯作者：
Thalmann,R
COL1A1 与耳硬化症的关联：轻度成骨不全症具有共同遗传病因的证据。
DOI：
--
发表时间：
1998
期刊：
The American journal of otology.
影响因子：
--
作者：
McKenna,MJ;Kristiansen,AG;Bartley,ML;Rogus,JJ;Haines,JL
通讯作者：
Haines,JL
影响因子：
6.9
作者：
Rossi, A;Kaitila, I;Superti-Furga, A
通讯作者：
Superti-Furga, A