We performed histochemical, immunohistochemical, electron-microscopic, and microchemical studies on cartilage growth plates from sixty-eight patients with nineteen different forms of human
osteochondrodysplasia. Cartilage biopsies were obtained during orthopaedic 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. This strongly suggested that in this syndrome an abnormal core
protein of a
proteoglycan species 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 three 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. This suggested that in this syndrome there is a structural alteration of the
type-II 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.
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