Risedronate Attenuates Podocyte Injury in Phosphate Transporter-Overexpressing Rats

Osteoporosis patients with chronic kidney disease (CKD) are becoming common in our superaging society. Renal dysfunction causes phosphorus accumulation in the circulating plasma and leads to the development of CKD-mineral bone disorder (MBD). We have previously reported that type III Pi transporter-...

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Main Authors: Yohei Asada, Takeshi Takayanagi, Tsukasa Kawakami, Eisuke Tomatsu, Atsushi Masuda, Yasumasa Yoshino, Sahoko Sekiguchi-Ueda, Megumi Shibata, Tomihiko Ide, Hajime Niimi, Eishin Yaoita, Yusuke Seino, Yoshihisa Sugimura, Atsushi Suzuki
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2019/4194853
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author Yohei Asada
Takeshi Takayanagi
Tsukasa Kawakami
Eisuke Tomatsu
Atsushi Masuda
Yasumasa Yoshino
Sahoko Sekiguchi-Ueda
Megumi Shibata
Tomihiko Ide
Hajime Niimi
Eishin Yaoita
Yusuke Seino
Yoshihisa Sugimura
Atsushi Suzuki
author_facet Yohei Asada
Takeshi Takayanagi
Tsukasa Kawakami
Eisuke Tomatsu
Atsushi Masuda
Yasumasa Yoshino
Sahoko Sekiguchi-Ueda
Megumi Shibata
Tomihiko Ide
Hajime Niimi
Eishin Yaoita
Yusuke Seino
Yoshihisa Sugimura
Atsushi Suzuki
author_sort Yohei Asada
collection DOAJ
description Osteoporosis patients with chronic kidney disease (CKD) are becoming common in our superaging society. Renal dysfunction causes phosphorus accumulation in the circulating plasma and leads to the development of CKD-mineral bone disorder (MBD). We have previously reported that type III Pi transporter-overexpressing transgenic (Pit-1 TG) rats manifest phosphate (Pi)-dependent podocyte injury. In the present study, we explored the effect of risedronate on Pi-induced podocyte injury in vivo. Pit-1 TG rats and wild-type rats at 5 weeks old were divided into a risedronate-treated group and an untreated group. We subcutaneously administered 5 μg/kg body weight of risedronate or saline twice a week during the experimental period. Risedronate did not alter serum creatinine levels at 5, 8, and 12 weeks of age. However, electron microscopy images showed that thickening of the glomerular basement membrane was improved in the risedronate treatment group. Furthermore, immunostaining for podocyte injury markers revealed that both desmin- and connexin43-positive areas were smaller in the risedronate-treated group than in the untreated group, suggesting that bisphosphonates could rescue Pi-induced podocyte injury. In conclusion, our findings suggest that risedronate could maintain glomerular barrier function by rescuing Pi-induced podocyte injury.
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spelling doaj-art-e626e3d2dc784acd9c8a2bfc164e6bca2025-02-03T01:11:13ZengWileyInternational Journal of Endocrinology1687-83371687-83452019-01-01201910.1155/2019/41948534194853Risedronate Attenuates Podocyte Injury in Phosphate Transporter-Overexpressing RatsYohei Asada0Takeshi Takayanagi1Tsukasa Kawakami2Eisuke Tomatsu3Atsushi Masuda4Yasumasa Yoshino5Sahoko Sekiguchi-Ueda6Megumi Shibata7Tomihiko Ide8Hajime Niimi9Eishin Yaoita10Yusuke Seino11Yoshihisa Sugimura12Atsushi Suzuki13Department of Endocrinology and Metabolism, Fujita Health University, Toyoake, Aichi 470-1192, JapanDepartment of Endocrinology and Metabolism, Fujita Health University, Toyoake, Aichi 470-1192, JapanDepartment of Endocrinology and Metabolism, Fujita Health University, Toyoake, Aichi 470-1192, JapanDepartment of Endocrinology and Metabolism, Fujita Health University, Toyoake, Aichi 470-1192, JapanDepartment of Endocrinology and Metabolism, Fujita Health University, Toyoake, Aichi 470-1192, JapanDepartment of Endocrinology and Metabolism, Fujita Health University, Toyoake, Aichi 470-1192, JapanDepartment of Endocrinology and Metabolism, Fujita Health University, Toyoake, Aichi 470-1192, JapanDepartment of Endocrinology and Metabolism, Fujita Health University, Toyoake, Aichi 470-1192, JapanJoint Research Support Promotion Facility, Center for Research Promotion and Support, Fujita Health University, Toyoake, Aichi 470-1192, JapanDepartment of Anatomy, Fujita Health University, Toyoake, Aichi 470-1192, JapanDepartment of Structural Pathology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 950-2102, JapanDepartment of Endocrinology and Metabolism, Fujita Health University, Toyoake, Aichi 470-1192, JapanDepartment of Endocrinology and Metabolism, Fujita Health University, Toyoake, Aichi 470-1192, JapanDepartment of Endocrinology and Metabolism, Fujita Health University, Toyoake, Aichi 470-1192, JapanOsteoporosis patients with chronic kidney disease (CKD) are becoming common in our superaging society. Renal dysfunction causes phosphorus accumulation in the circulating plasma and leads to the development of CKD-mineral bone disorder (MBD). We have previously reported that type III Pi transporter-overexpressing transgenic (Pit-1 TG) rats manifest phosphate (Pi)-dependent podocyte injury. In the present study, we explored the effect of risedronate on Pi-induced podocyte injury in vivo. Pit-1 TG rats and wild-type rats at 5 weeks old were divided into a risedronate-treated group and an untreated group. We subcutaneously administered 5 μg/kg body weight of risedronate or saline twice a week during the experimental period. Risedronate did not alter serum creatinine levels at 5, 8, and 12 weeks of age. However, electron microscopy images showed that thickening of the glomerular basement membrane was improved in the risedronate treatment group. Furthermore, immunostaining for podocyte injury markers revealed that both desmin- and connexin43-positive areas were smaller in the risedronate-treated group than in the untreated group, suggesting that bisphosphonates could rescue Pi-induced podocyte injury. In conclusion, our findings suggest that risedronate could maintain glomerular barrier function by rescuing Pi-induced podocyte injury.http://dx.doi.org/10.1155/2019/4194853
spellingShingle Yohei Asada
Takeshi Takayanagi
Tsukasa Kawakami
Eisuke Tomatsu
Atsushi Masuda
Yasumasa Yoshino
Sahoko Sekiguchi-Ueda
Megumi Shibata
Tomihiko Ide
Hajime Niimi
Eishin Yaoita
Yusuke Seino
Yoshihisa Sugimura
Atsushi Suzuki
Risedronate Attenuates Podocyte Injury in Phosphate Transporter-Overexpressing Rats
International Journal of Endocrinology
title Risedronate Attenuates Podocyte Injury in Phosphate Transporter-Overexpressing Rats
title_full Risedronate Attenuates Podocyte Injury in Phosphate Transporter-Overexpressing Rats
title_fullStr Risedronate Attenuates Podocyte Injury in Phosphate Transporter-Overexpressing Rats
title_full_unstemmed Risedronate Attenuates Podocyte Injury in Phosphate Transporter-Overexpressing Rats
title_short Risedronate Attenuates Podocyte Injury in Phosphate Transporter-Overexpressing Rats
title_sort risedronate attenuates podocyte injury in phosphate transporter overexpressing rats
url http://dx.doi.org/10.1155/2019/4194853
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