Poole A R, Pidoux I, Reiner A, Rosenberg L, Hollister D, Murray L, Rimoin D
Shriners Hospital for Crippled Children, Department of Experimental Surgery, McGill University, Montreal, Quebec, Canada.
J Clin Invest. 1988 Feb;81(2):579-89. doi: 10.1172/JCI113356.
Epiphyseal and growth plate cartilages from four cases of Kniest dysplasia have been studied. In each case collagen fibril organization appeared abnormal by electron microscopy compared with age-matched normal cartilages: fibrils were much thinner, of irregular shape and did not exhibit the characteristic banding pattern. This was associated with the absence (compared with normal cartilage) of the C-propeptide of type II collagen (chondrocalcin) from the extracellular matrix of epiphyseal cartilages, although it was detected (as in normal cartilages) in the lower hypertrophic zone of the growth plate in association with calcifying cartilage. The C-propeptide was abnormally concentrated in intracellular vacuolar sites in Kniest cartilages and its total content was reduced in all cases but not in all cartilages. Moreover, it was not a part of the procollagen molecule. In contrast, type II collagen alpha-chain size was normal, indicating the formation of a triple helix. Also type II collagen content was normal and it was present in extracellular sites and only occasionally detected intracellularly. These observations suggest that the defect in Kniest dysplasia may result from the secretion of type II procollagen lacking the C-propeptide and abnormal fibril formation, and that the C-propeptide is normally required for fibril formation.
对4例Kniest发育不良患者的骨骺和生长板软骨进行了研究。与年龄匹配的正常软骨相比，通过电子显微镜观察，每例患者的胶原纤维组织均出现异常：纤维更细，形状不规则，且未呈现特征性的带状模式。这与骨骺软骨细胞外基质中II型胶原（软骨钙素）的C-前肽缺失（与正常软骨相比）有关，尽管在生长板的较低肥大带中与钙化软骨相关联处可检测到C-前肽（如同在正常软骨中一样）。在Kniest软骨中，C-前肽异常集中在细胞内的液泡部位，其总含量在所有病例中均降低，但并非在所有软骨中都降低。此外，它不是原胶原分子的一部分。相比之下，II型胶原α链大小正常，表明形成了三螺旋结构。II型胶原含量也正常，存在于细胞外部位，仅偶尔在细胞内检测到。这些观察结果表明，Kniest发育不良中的缺陷可能是由于缺乏C-前肽的II型前胶原分泌以及异常的纤维形成所致，并且C-前肽通常是纤维形成所必需的。
