Rao V H, Buehler B A, Schaefer G B
Matrix Research Laboratory, Munroe Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha 68198, USA.
Clin Biochem. 1998 Jun;31(4):241-9. doi: 10.1016/s0009-9120(98)00023-x.
To investigate whether the advanced bone age in Sotos syndrome is associated with alterations in type I collagen metabolism in bone.
The metabolism of collagen was studied by analyzing the production, gene expression and degradation of type I collagen in dermal fibroblast strains from patients with Sotos syndrome and comparing them with fibroblasts from age-matched healthy subjects. Collagen production was determined as collagenase digestible radioactivity and collagen mRNA levels were measured by RT-PCR. Collagen degradation was assessed by specific collagenase assay and gelatin zymography. To determine the structural defects in type I collagen, the newly synthesized proteins were analyzed by SDS-PAGE before and after proteolytic digestion with pepsin.
In the present study, we have demonstrated that the collagen production, secretion and degradation in Sotos syndrome is comparable to controls. In addition, no qualitative differences in mRNA transcripts for type I collagen were detected between the control and Sotos syndrome fibroblasts. The secretion and intracellular accumulation of procollagen is also comparable to controls. The analysis of both procollagen and collagen on SDS-PAGE did not exhibit any major structural changes as compared with controls.
Our results on several aspects of collagen metabolism have demonstrated for the first time that collagen, the most abundant of mammalian proteins and the major constituent of bone, is normal in patients with Sotos syndrome. Therefore, it appears that the advanced bone age and accelerated linear growth seen in patients with Sotos syndrome may not be attributed to inherent abnormalities of collagen metabolism. The etiology and the pathogenesis of Sotos syndrome still remains unclear.
研究索托斯综合征（Sotos syndrome）中骨龄提前是否与骨中I型胶原代谢改变有关。
通过分析索托斯综合征患者皮肤成纤维细胞系中I型胶原的产生、基因表达和降解，并将其与年龄匹配的健康受试者的成纤维细胞进行比较，研究胶原的代谢。胶原产生以胶原酶可消化放射性来确定，胶原mRNA水平通过逆转录聚合酶链反应（RT-PCR）测量。胶原降解通过特异性胶原酶测定和明胶酶谱法评估。为了确定I型胶原的结构缺陷，在胃蛋白酶进行蛋白水解消化前后，通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）分析新合成的蛋白质。
在本研究中，我们已证明索托斯综合征中胶原的产生、分泌和降解与对照组相当。此外，在对照组和成纤维细胞系之间未检测到I型胶原mRNA转录本的定性差异。前胶原的分泌和细胞内积累也与对照组相当。与对照组相比，SDS-PAGE上对前胶原和胶原的分析未显示任何主要结构变化。
我们在胶原代谢几个方面的结果首次证明，作为哺乳动物中最丰富的蛋白质和骨的主要成分的胶原，在索托斯综合征患者中是正常的。因此，看来索托斯综合征患者中出现的骨龄提前和线性生长加速可能不能归因于胶原代谢的内在异常。索托斯综合征的病因和发病机制仍不清楚。
