Growth Plate Cartilage Formation and Resorption Are Differentially Depressed in Growth Retarded Uremic Rats

Abstract

Abstract. To characterize the modifications of growth plate in individuals with growth impairment secondary to chronic renal failure, young rats were made uremic by subtotal nephrectomy (NX) and, after 14 d, their tibial growth plates were studied and compared with those of sham-operated rats fed ad libitum (SAL) or pair-fed with NX (SPF). NX rats were growth retarded and severely uremic. Growth plate height (mean ± SD) was much greater (P < 0.05) in NX (868.4 ± 85.4 μm) than SAL (570.1 ± 93.5 μm) and SPF (551.9 ± 99.7 μm) rats as a result of a higher (P < 0.05) hypertrophic zone (661.0 ± 89.7 versus 362.8 ± 71.6 and 353.0 ± 93.9 μm, respectively). The increased size of the growth plate was associated with a greater number of chondrocytes and modifications in their structure, particularly in the hypertrophic zone adjacent to bone. In this zone, chondrocytes of NX animals were significantly (P < 0.05) smaller (12080.4 ± 1158.3 μm3) and shorter (34.1 ± 2.5 μm) than those of SAL (16302.8 ± 1483.4 μm3 and 37.8 ± 2.0 μm) and SPF (14465.8 ± 1521.0 μm3 and 36.3 ± 1.8 μm). The interface between the growth plate cartilage and the metaphyseal bone appeared markedly irregular in NX rats. Kinetics of chondrocytes was also modified (P < 0.05) in the NX rats, which had lower cell turnover per column per day (5.4 ± 0.9), longer duration of hypertrophic phase (89.0 ± 15.2 h), and reduced cellular advance velocity (7.4 ± 2.2 μm/h) compared with SAL (8.0 ± 1.6, 32.1 ± 6.7 h, and 11.3 ± 2.7 μm/h) and SPF (7.2 ± 1.1, 34.8 ± 5.1 h, and 10.1 ± 2.5 μ/h). Cell proliferation was no different among the three groups. Because the growth plates of SPF and SAL rats were substantially not different, modifications observed in the NX rats cannot be attributed to the nutritional deficit associated with renal failure. These findings indicate that chronic renal failure depresses both the activity of the growth plate cartilage by altering chondrocyte hypertrophy and the replacement of cartilage by bone at the metaphyseal end. The two processes are differentially depressed since cartilage resorption is more severely lowered than cartilage enlargement and this leads to an accumulation of cartilage at the hypertrophic zone.