Collagen metabolism is markedly altered in the hypertrophic cartilage of growth plates from rats with growth impairment secondary to chronic renal failure

Skeletal growth depends on growth plate cartilage activity, in which matrix synthesis by chondrocytes is one of the major processes contributing to th e final length of a bone. On this basis, the present work was undertaken to ascertain if growth impairment secondary to chronic renal insufficiency is associated with disturbances of the extracellular matrix (ECM) of the grow th plate. By combining stereological and in situ hybridization techniques, we examined the expression patterns of types II and X collagens and collage nase-3 in tibial growth plates of rats made uremic by subtotal nephrectomy (NX) in comparison with those of sham-operated rats fed ad libitum (SAL) an d sham-operated rats pair-fed with NX (SPF), NX rats were severely uremic, as shown by markedly elevated serum concentrations of urea nitrogen, and gr owth retarded, as shown by significantly decreased longitudinal bone growth rates. NX rats showed disturbances in the normal pattern of chondrocyte di fferentiation and in the rates and degree of substitution of hypertrophic c artilage with bone, which resulted in accumulation of cartilage at the hype rtrophic zone. These changes were associated with an overall decrease in th e expression of types n and X collagens, which was especially marked in the abnormally extended zone of the hypertrophic cartilage. Unlike collagen, t he expression of collagenase-3 was not disturbed severely. Electron microsc opic analysis proved that changes in gene expression were coupled to altera tions in the mineralization as well as in the collagen fibril architecture at the hypertrophic cartilage. Because the composition and structure of the ECM have a critical role in regulating the behavior of the growth plate ch ondrocytes, results obtained are consistent with the hypothesis that altera tion of collagen metabolism in these cells could be a key process underlyin g growth retardation in uremia.