Alterations in the growth plate cartilage of rats with renal failure receiving corticosteroid therapy.
Growth retardation is a complication often associated with corticosteroid therapy. Corticosteroids are frequently used in the treatment of children with chronic renal failure. To examine the effects of corticosteroids on the growth plate cartilage in renal failure, selected markers of chondrocyte function and phenotype were evaluated in the proximal tibia of subtotally nephrectomized rats treated with corticosteroid. Serum parathyroid hormone (PTH), urea nitrogen, and creatinine levels were higher in the nephrectomized animals. Weight gain was less in the corticosteroid-treated animals; however, linear growth and tibial length did not differ among the groups after 10 days of corticosteroid therapy. The total width of the growth plate and the width of the proliferative zone were much smaller in corticosteroid-treated nephrectomized (Nx-MP) animals. Type II collagen mRNA expression was lower in animals treated with corticosteroids, and proliferating-cell nuclear antigen staining, histone-4, and insulin-like growth factor-1 (IGF-1)-receptor mRNA expression were further decreased in the Nx-MP group. There was an increase in TUNEL-positive cells in the corticosteroid-treated rats with normal renal function (intact-MP), associated with an increase in Bax and a decrease in Bcl-2 protein expression. In the Nx-MP group, both Bax and Bcl-2 protein staining was much less frequent, and TUNEL-positive cells were lower in number compared with the intact-MP group. Vascular endothelial growth factor expression in the hypertrophic chondrocytes was lower in corticosteroid-treated animals. There was less gelatinase B/matrix metalloproteinase-9 expression in the Nx-MP group, which was not associated with a decrease in tartrate-resistant acid phosphatase (TRAP) staining in the chondro-osseous junction. Inhibition of chondrocyte proliferation, diminishing of apoptosis, and lower angiogenic activity may contribute to the alterations in growth plate architecture and the significant reduction in growth plate width in rats with renal failure receiving corticosteroid therapy.
Sanchez
Cheryl P
CP
Department of Pediatrics, University of Wisconsin Medical School, 1300 University Avenue, Madison, WI 53706, USA. cpsanchez@facstaff.wisc.edu
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D000818:Animals; D001806:Blood Urea Nitrogen; D002455:Cell Division; D019902:Chondrocytes / Q000473:pathology; D024043:Collagen Type II / Q000235:genetics; D003404:Creatinine / Q000097:blood; D016228:Endothelial Growth Factors / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006132:Growth Plate / Q000187:drug effects / Q000254:growth & development / Q000473:pathology*; D006657:Histones / Q000235:genetics; D006984:Hypertrophy; D020287:In Situ Nick-End Labeling; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000188:drug therapy*; D008222:Lymphokines / Q000235:genetics; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D009392:Nephrectomy; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D024043:Collagen Type II; D016228:Endothelial Growth Factors; D005938:Glucocorticoids; D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003404:Creatinine; D017526:Receptor, IGF Type 1; D008775:Methylprednisolone