Synthesis of abnormal articular cartilage proteoglycans in rapidly destructive arthropathy (osteoarthritis)

Abstract

Articular cartilage fragments were obtained from four femoral heads and one femoral condyle, resected in five patients undergoing prosthetic surgery for rapidly destructive arthropathy (RDA) and from one normal femoral head and one normal femoral condyle resected at autopsy. The cartilage fragments were labelled in vitro with 35SO4 and newly-synthesized proteoglycans, (35S-PGs) were then extracted with 4 M guanidinium hydrochloride (GuHCl) and analyzed. In three cases a much greater and in one case a significantly increased proportion of small 35S-PGs enriched in dermatan sulfate (DS) was demonstrated in diseased tissues in comparison with control samples. These DS 35S-PGs were completely unable to interact with hyaluronan (HA) and had longer glycosamino-glycan (GAG) side chains than large 35S-PGs. Also, large 35S-PGs extracted from diseased tissue interacted poorly under associative conditions with exogenous HA when this was added to the crude extract. However, they interacted much better following the addition of exogenous HA to the purified high density proteoglycans. This suggests the presence of an inhibitor of PG-HA interaction in the crude extract which is lost during PG purification. The synthesis of an abnormally large proportion of small PGs by articular chondrocytes and impaired aggregation of large PGs may account for the accelerated destruction of articular cartilage in this condition.