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

• Main Authors: Cai-Mei Zheng, Yung-Ho Hsu, Chia-Chao Wu, Chien-Lin Lu, Wen-Chih Liu, Jing-Quan Zheng, Yuh-Feng Lin, Hui-Wen Chiu, Tian-Jong Chang, Jia-Fwu Shyu, Kuo-Cheng Lu
• Format: Article
• Language: English
• Published: MDPI AG 2019-06-01
• Series: International Journal of Molecular Sciences
• Subjects: cinacalcet; renal osteodystrophy; osteoclast; Wnt 10b; chronic kidney disease
• Online Access: https://www.mdpi.com/1422-0067/20/11/2800

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.