Pathogenic mechanisms in osteochondrodysplasias
Stanescu, V.; Stanescu, R.; Maroteaux, P.
Journal of Bone and Joint Surgery. American Volume 66(6): 817-836
1984
ISSN/ISBN: 0021-9355 PMID: 6376516 Document Number: 236224
Histochemical, immunohistochemical, EM and microchemical studies were performed on cartilage growth plates from 68 patients with 19 different forms of human osteochondrodysplasia. Cartilage biopsies were obtained during orthopedic procedures. Postmortem specimens were obtained within a short time after death. The combined morphological and biochemical studies revealed specific abnormalities suggestive of a particular biochemical defect in several chondrodysplasias. In pseudoachondroplasia, non-collagenous protein accumulated in the rough endoplasmic reticulum of chondrocytes and a proteoglycan species that normally is present in the extracellular matrix was not detected by gel electrophoresis. The accumulated material was stained with antibodies against the core protein of proteoglycan. In this syndrome an abnormal core protein of a proteoglycan species evidently is not properly transferred to the Golgi system. In Kniest syndrome, intracytoplasmic accumulation of metachromatic material, dilatation of rough endoplasmic reticulum, and an abnormal gel-electrophoretic pattern of cartilage proteoglycans suggested an abnormality of cartilage proteoglycan metabolism. Abnormalities that probably are related to degradative lysosomal processes of proteoglycans in chondrocytes were found in spondylometaphyseal dysplasia of the Kozlowski type. An abnormal organization of type-II collagen was found in fibrochondrogenesis. In diastrophic dysplasia, an abnormal organization of collagen was found in areas of interterritorial matrix and around many degenerated cells, but also in the lacunae of cells without ultrastructural signs of degeneration. The segment-long-spacing form of collagen prepared from cartilage of 3 patients with diastrophic dysplasia showed an abnormal cross-striation pattern in a portion between bands 42 and 45, corresponding to the position of the .alpha.1(II) cyanogen-bromide-derived 10,5 peptide. In this syndrome there is a structural alteration of the type-11 collagen molecule. There was an accumulation of intracellular lipid in pyknodysostosis and in hypochondrogenesis, and of glycoproteins in several atypical cases of spondyloepiphyseal dysplasia. In a pair of twins with an atypical form of spondyloepiphyseal dysplasia, the presence of many multinucleated chondrocytes suggested a primary impairment of cell division.