The Journal of Bone and Joint Surgery, Vol 66, Issue 6 817-836, Copyright © 1984 by Journal of Bone and Joint Surgery, Inc
Pathogenic mechanisms in osteochondrodysplasias
V Stanescu, R Stanescu and P Maroteaux
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. Clinical Relevance: A knowledge of the pathogenic mechanisms in
osteochondrodysplasias might improve the classification; aid in diagnosis,
prognosis, and genetic counseling; and contribute to the understanding of
normal endochondral growth.(ABSTRACT TRUNCATED AT 400 WORDS)
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