Brenner R E, Vetter U, Nerlich A, Wörsdorfer O, Teller W M, Müller P K
Max Planck Institut für Biochemie, Martinsried, FRG.
Eur J Clin Invest. 1990 Feb;20(1):8-14. doi: 10.1111/j.1365-2362.1990.tb01785.x.
The pattern of collagen metabolism was analysed in fibroblast cultures from patients with diverse forms of osteogenesis imperfecta (OI). Generally, OI fibroblasts show an insufficient collagen synthesis which is most obvious in patients between 2 and 9 years of age during which period control fibroblasts have an elevated collagen synthesis. OI fibroblasts remain on a basal level except for fibroblasts from OI type IV patients which seem to approach normal levels. In addition, OI fibroblasts generally show a slightly increased degradation of newly synthesized collagen which again is most obvious between 2 and 9 years. These differences in collagen degradation, however, only contribute to a minor extent to the lack of net collagen synthesis during early childhood. No correlation could be found between the degree of overmodification of collagen and its degradation since fibroblasts of both OI type I and OI type II have an elevated degradation though only the latter ones produce overmodified collagen molecules. Pulse labelling of collagen with radioactivity labelled sugars was used to distinguish between normal collagen chains or CNBr-derived peptides and those which were overmodified. In all three cases studied (OI II, OI III, OI IV) the entire triple helical domain of alpha 1(I) and alpha 2(I) was overglycosylated. The amount of overmodification, however, was not uniform but rather unique for each patient studied. We assume that the molecular defects in the majority of OI cases may be located in the mechanisms operating on the control of both the age appropriate synthesis of collagen and its degree of post-translational modification.
对多种类型成骨不全症（OI）患者的成纤维细胞培养物中的胶原蛋白代谢模式进行了分析。一般来说，OI成纤维细胞显示出胶原蛋白合成不足，这在2至9岁的患者中最为明显，在此期间对照成纤维细胞的胶原蛋白合成有所增加。除了IV型OI患者的成纤维细胞似乎接近正常水平外，OI成纤维细胞保持在基础水平。此外，OI成纤维细胞通常显示出新合成胶原蛋白的降解略有增加，这在2至9岁之间再次最为明显。然而，这些胶原蛋白降解的差异仅在较小程度上导致幼儿期净胶原蛋白合成的缺乏。由于I型OI和II型OI的成纤维细胞都有较高的降解，尽管只有后者产生过度修饰的胶原蛋白分子，但胶原蛋白的过度修饰程度与其降解之间没有相关性。用放射性标记的糖对胶原蛋白进行脉冲标记，以区分正常的胶原蛋白链或CNBr衍生的肽与那些过度修饰的肽。在所研究的所有三种情况（OI II、OI III、OI IV）中，α1（I）和α2（I）的整个三螺旋结构域都过度糖基化。然而，过度修饰的量并不均匀，而是每个研究患者都有其独特性。我们假设，大多数OI病例的分子缺陷可能位于控制胶原蛋白年龄适当合成及其翻译后修饰程度的机制中。
