Growth plate cartilage formation and resorption are differentially depressed in growth retarded uremic rats

To characterize the modifications of growth plate in individuals with growt h impairment secondary to chronic renal failure, young rats were made uremi c 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 u remic. Growth plate height (mean +/- SD) was much greater (P < 0.05) in NX (868.4 +/- 85.4 mu m) than SAL (570.1 +/- 93.5 mu m) and SPF (551.9 +/- 99. 7 mu m) 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 mu m, respectively). The in creased size of the growth plate was associated with a greater number of ch ondrocytes and modifications in their structure, particularly in the hypert rophic zone adjacent to bone. In this zone, chondrocytes of NX animals were significantly (P < 0.05) smaller (12080.4 +/- 1158.3 mu m(3)) and shorter (34.1 +/- 2.5 mu m) than those of SAL (16302.8 +/- 1483.4 mu m(3) and 37.8 +/- 2.0 mu m) and SPF (14465.8 +/- 1521.0 mu m(3) and 36.3 +/- 1.8 mu m). T he interface between the growth plate cartilage and the metaphyseal bone ap peared markedly irregular in NX rats. Kinetics of chondrocytes was also mod ified (P < 0.05) in the NX rats, which had lower cell turnover per column p er day (5.4 +/- 0.9), longer duration of hypertrophic phase (89.0 +/- 15.2 h), and reduced cellular advance velocity (7.4 +/- 2.2 mu m/h) compared wit h SAL (8.0 +/- 1.6, 32.1 +/- 6.7 h, and 11.3 +/- 2.7 mu m/h) and SPF (7.2 /- 1.1, 34.8 +/- 5.1 h, and 10.1 +/- 2.5 mu m/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 ra ts cannot be attributed to the nutritional deficit associated with renal fa ilure. These findings indicate that chronic renal failure depresses both th e activity of the growth plate cartilage by altering chondrocyte hypertroph y and the replacement of cartilage by bone at the metaphyseal end. The two processes are differentially depressed since cartilage resorption is more s everely lowered than cartilage enlargement and this leads to an accumulatio n of cartilage at the hypertrophic zone.