Early molecular responses of bone to obstructive nephropathy induced by unilateral ureteral obstruction in mice
Article first published online: 29 OCT 2012
© 2012 The Authors. Nephrology © 2012 Asian Pacific Society of Nephrology
Volume 17, Issue 8, pages 767–773, November 2012
How to Cite
GU, S.-S., ZHANG, Y., WU, S.-Y., DIAO, T.-Y., GEBRU, Y. A. and DENG, H.-W. (2012), Early molecular responses of bone to obstructive nephropathy induced by unilateral ureteral obstruction in mice. Nephrology, 17: 767–773. doi: 10.1111/j.1440-1797.2012.01656.x
- Issue published online: 29 OCT 2012
- Article first published online: 29 OCT 2012
- Accepted manuscript online: 4 SEP 2012 01:58AM EST
- Accepted for publication 21 August 2012.; Accepted manuscript online 4 September 2012.
- angiotensin II;
- renal osteodystrophy;
- renin-angiotensin system;
- unilateral ureteral obstruction
Aim: This study was performed to address the bone injury and the early molecular responses of bone to obstructive nephropathy induced by unilateral ureteral obstruction in mice.
Methods: The male mice were subjected to unilateral ureteral obstruction (UUO, n = 10) or sham operation (n = 10). All mice were killed on day 7 after the surgical operation. Hematoxylin and eosin and tartate-resistant acid phosphatase staining were performed on paraffin-embedded bone sections. Expression of genes and proteins was analyzed by reverse transcription-polymerase chain reaction, and Western blotting and immunohistochemistry staining, respectively.
Results: The serum calcium level was significantly reduced in UUO mice compared with that of Sham mice. The proximal tibia of UUO mice exhibited the increased expansion of chondrocytes zone, the reduction of osteoid content, and the increased separation and disconnection of woven bones. Reverse transcription-polymerase chain reaction results showed the downregulation of Cbfa1 and Col mRNA expression and the upregulation of Tgf-β, CtsK, CaII, Opg and Rankl mRNA expression in tibia of UUO mice compared to those of Sham mice. The ratio of Opg and Rankl was unchanged between Sham and the UUO group. Local protein expression of angiotensin II and its type 2 receptor was dramatically upregulated in tibia of UUO mice.
Conclusion: Together, it is concluded that the obstructive nephropathy has defective effects on bone, and the underlying mechanisms are the reduction of bone formation and the increase of bone resorption, which is mediated, at least partially through local angiotensin II signalling.