Early molecular responses of bone to obstructive nephropathy induced by unilateral ureteral obstruction in mice

Abstract

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.