Does crystal deposition in genetic hypercalciuric rat kidney tissue share similarities with bone formation?
OBJECTIVE
To address the effect of bone-related factors and 1,25(OH)2D3/vitamin D receptor (VDR) on renal stone formation in idiopathic hypercalciuria using genetic hypercalciuric rats.


METHODS
The basal levels of bone-related factors were detected in Sprague-Dawley and genetic hypercalciuric rats. In VDR silenced kidneys, the expression levels of bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (Runx2), Osterix, and osteopontin (OPN) were measured, respectively. Tubular calcium phosphate deposits in kidneys and renal tubular epithelial cells (RTECs) were assessed using von Kossa stain. Kidneys were stained with immunohistochemical staining for OPN expression. Gene and protein expression levels of BMP2, Runx2, and Osterix were examined in RTECs incubated with 1,25(OH)2D3.


RESULTS
The basal levels of BMP2, Runx2, Osterix, and OPN were significantly increased in genetic hypercalciuric rats, whereas there were no differences in the expression levels of msh homeobox homolog 2 and alkaline phosphatase between the genetic hypercalciuric and normal control rats. VDR knockdown in genetic hypercalciuric rats reduced the expression levels of BMP2, Runx2, Osterix, and OPN. Tubular calcium phosphate deposits were also decreased in VDR silenced kidneys. Immunohistochemical staining showed that there was a reduction in OPN expression in RTECs along with reduction in calcification. Gene and protein expression levels of BMP2, Runx2, and Osterix were upregulated in RTECs incubated with 1,25(OH)2D3. The calcium phosphate deposits in RTECs were also increased by elevated 1,25(OH)2D3.


CONCLUSIONS
Our findings indicate that BMP2, Runx2, Osterix, and OPN might play an important role in renal stone formation in idiopathic hypercalciuria, and 1,25(OH)2D3/VDR might be the significant regulator in this process.
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Zhaohui
Z
Jia
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China. Electronic address: sgwangtjm@163.com.
Shaogang
S
Wang
Department of Paediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China. Electronic address: jinhuitangwuhan@163.com.
Jinhui
J
Tang
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Deng
D
He
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Lei
L
Cui
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Zhenyu
Z
Liu
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Bingtao
B
Guo
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Lei
L
Huang
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Yuchao
Y
Lu
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Henglong
H
Hu
D000818:Animals; D003460:Crystallization; D005260:Female; D053565:Hypercalciuria / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007669:Kidney Calculi / Q000209:etiology / Q000235:genetics*; D008297:Male; D010012:Osteogenesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000502:physiology
D018167:Receptors, Calcitriol