Expression of bone type 1 PTH receptor in rats with chronic renal failure.
Some researchers have speculated that a decrease in bone type 1 PTH receptor (PTH1R) may be among the causes of "skeletal resistance" in chronic renal failure (CRF). Indeed, the down-regulation of PTH1R mRNA has been identified in uremic bones. However, few studies have identified the patterns of PTH1R protein expression. In this article we compare the bone expression of PTH1R protein and mRNA under control and CRF conditions. Sprague-Dawley rats underwent 5/6 nephrectomies (Nx) or sham operations (control), and were killed 16 weeks later. Blood urea nitrogen (BUN), serum Cr, P, and parathyroid hormone (PTH) were higher in the Nx group than in the controls, while serum Ca and 1,25(OH)(2)D(3) were lower in the Nx group. Immunohistochemical images of lumbar bone samples were analyzed by an image processing system. PTH1R was essentially identified in all osteoblasts. The expression of osteoblast PTH1R protein was quantified based on the gray value of PTH1R staining. The mean gray scale of osteoblasts was 25% lower in Nx rats than in control rats (P < 0.01), whereas osteoblast cell counts and cell sizes were not significantly different between the two groups. Thus, down-regulation of PTH1R protein expression under the CRF condition appeared likely. Total RNA extracted from the bone samples was reverse transcribed for real-time polymerase chain reaction (PCR). PTH1R mRNA expression was 33% lower in the Nx group than in the control group in the quantitative PCR analysis (P < 0.05). Our findings suggested that osteoblast PTH1R expression is down-regulated at both the protein and mRNA levels in the steady state of CRF.
Kuwahara
Michio
M
Division of Nephrology, Shuwa General Hospital, 1200 Yahara-Shinden, Kasukabe, Saitama 344-0035, Japan. kuwaharam@shuwa.or.jp
Inoshita
Seiji
S
Nakano
Yukiko
Y
Terada
Yoshio
Y
Takano
Yoshiro
Y
Sasaki
Sei
S
D000818:Animals; D015870:Gene Expression; D006962:Hyperparathyroidism, Secondary / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008159:Lumbar Vertebrae / Q000378:metabolism*; D008297:Male; D009392:Nephrectomy; D010006:Osteoblasts / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism*
D044168:Receptor, Parathyroid Hormone, Type 1