Zhaohui Jia1, Shaogang Wang2, Jinhui Tang3, Deng He1, Lei Cui1, Zhenyu Liu1, Bingtao Guo1, Lei Huang1, Yuchao Lu1, Henglong Hu1. 1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China. 2. 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. 3. 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.
Abstract
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. CONCLUSION: 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.
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. CONCLUSION: 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.
Authors: Ivan Lau; Ajay Potluri; Cliff-Lawrence Ibeh; Robert S Redman; Edina Paal; Bidhan C Bandyopadhyay Journal: Arch Oral Biol Date: 2017-06-07 Impact factor: 2.633
Authors: Saeed R Khan; Margaret S Pearle; William G Robertson; Giovanni Gambaro; Benjamin K Canales; Steeve Doizi; Olivier Traxer; Hans-Göran Tiselius Journal: Nat Rev Dis Primers Date: 2016-02-25 Impact factor: 52.329