Next Article in Journal
Quantitative Structure–Activity Relationships for Structurally Diverse Chemotypes Having Anti-Trypanosoma cruzi Activity
Previous Article in Journal
Scavenging of Retinoid Cation Radicals by Urate, Trolox, and α-, β-, γ-, and δ-Tocopherols
Previous Article in Special Issue
Novel Peptide-Based Inhibitors for Microtubule Polymerization in Phytophthora capsici
Open AccessArticle

Osteoclast-Released Wnt-10b Underlies Cinacalcet Related Bone Improvement in Chronic Kidney Disease

1
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
2
Division of Nephrology, Department of Internal Medicine, School of Medicine, Taipei Medical University, New Taipei City 235, Taiwan
3
Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan
4
Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 10581, Taiwan
5
Division of Nephrology, Department of Medicine, Fu Jen Catholic University Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City 243, Taiwan
6
Division of Nephrology, Department of Internal Medicine, Tungs’ Taichung Metroharbor Hospital, Taichung City 43304, Taiwan
7
Department of Critical Care Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei 235, Taiwan
8
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan
9
Performance Appraisal Section, Secretary Office, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan
10
Department of Biology and Anatomy, National Defense Medical Center, Taipei 110, Taiwan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(11), 2800; https://doi.org/10.3390/ijms20112800
Received: 9 May 2019 / Revised: 29 May 2019 / Accepted: 6 June 2019 / Published: 8 June 2019
(This article belongs to the Special Issue Enzymes as Targets for Drug Development)
Secondary hyperparathyroidism (SHPT) relates to high turnover bone loss and is responsible for most bone fractures among chronic kidney disease (CKD) patients. Changes in the Wingless/beta-catenin signaling (Wnt/β-catenin) pathway and Wnt inhibitors have been found to play a critical role in CKD related bone loss. A calcimimetic agent, cinacalcet, is widely used for SHPT and found to be similarly effective for parathyroidectomy clinically. A significant decrease in hip fracture rates is noted among US hemodialysis Medicare patients since 2004, which is probably related to the cinacalcet era. In our previous clinical study, it was proven that cinacalcet improved the bone mineral density (BMD) even among severe SHPT patients. In this study, the influence of cinacalcet use on bone mass among CKD mice was determined. Cinacalcet significantly reduced the cortical porosity in femoral bones of treated CKD mice. It also improved the whole-bone structural properties through increased stiffness and maximum load. Cinacalcet increased femoral bone wingless 10b (Wnt10b) expression in CKD mice. In vitro studies revealed that cinacalcet decreased osteoclast bone resorption and increased Wnt 10b release from osteoclasts. Cinacalcet increased bone mineralization when culturing the osteoblasts with cinacalcet treated osteoclast supernatant. In conclusion, cinacalcet increased bone quantity and quality in CKD mice, probably through increased bone mineralization related with osteoclast Wnt 10b secretion. View Full-Text
Keywords: cinacalcet; renal osteodystrophy; osteoclast; Wnt 10b; chronic kidney disease cinacalcet; renal osteodystrophy; osteoclast; Wnt 10b; chronic kidney disease
Show Figures

Graphical abstract

MDPI and ACS Style

Zheng, C.-M.; Hsu, Y.-H.; Wu, C.-C.; Lu, C.-L.; Liu, W.-C.; Zheng, J.-Q.; Lin, Y.-F.; Chiu, H.-W.; Chang, T.-J.; Shyu, J.-F.; Lu, K.-C. Osteoclast-Released Wnt-10b Underlies Cinacalcet Related Bone Improvement in Chronic Kidney Disease. Int. J. Mol. Sci. 2019, 20, 2800.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop