Downregulation of parathyroid hormone receptor gene expression and osteoblastic dysfunction associated with skeletal resistance to parathyroid hormone in a rat model of renal failure with low turnover bone

Autor: Hideyuki Yamato, Kiyoshi Kurokawa, Masafumi Fukagawa, Tomoko Nii-Kono, Yoshiko Iwasaki-Ishizuka
Rok vydání: 2005
Předmět:
Zdroj: Nephrology Dialysis Transplantation. 20:1904-1911
ISSN: 1460-2385
0931-0509
DOI: 10.1093/ndt/gfh876
Popis: Background. Adynamic bone disease (ABD), which is characterized by reduced bone formation and resorption, has become an increasingly common manifestation of bone abnormalities in patients with end-stage renal failure. It has been recognized that skeletal resistance to parathyroid hormone (PTH) underlies the pathogenesis of ABD; however, the mechanisms of such resistance remain unclear. Methods. We established a rat model simulating ABD under chronic renal failure conditions by thyroparathyroidectomy and partial nephrectomy (TPTxNx). TPTx-Nx rats were infused subcutaneously with a physiological dose of PTH. We analysed bone histomorphometric parameters and demonstrated gene expression using semi-quantitative reverse transcription–polymerase chain reaction. Results. Reduced bone formation was observed in this model, simulating ABD. The reduction was dependent on the degree of renal dysfunction. Bone formation rate was 6.4±2.7mm 3 /m 2 /year in TPTx5/6Nx rats and 22.7±7.2mm 3 /m 2 /year in TPTx rats (P
Databáze: OpenAIRE