Abstract: SA-PO896

Cinacalcet Attenuates Bone Loss in CKD through Preventing the Endothelial to Adipocyte Transition

Session Information

  • Mineral Disease: CKD-Bone
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Mineral Disease

  • 1203 Mineral Disease: CKD-Bone

Authors

  • Ni, Li-Hua, Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, China, Nanjing, jiangsu, China
  • tang, rining, Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, China, Nanjing, jiangsu, China
  • Song, Kaiyun, Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, China, Nanjing, jiangsu, China
  • Liu, Bi-Cheng, Zhong Da Hospital, Southeast University Medical School, Nanjing, JIANGSU , China
Background

Recently, cinacalcet (CINA) has been proved to be beneficial to bone lose in chronic kidney disease (CKD), while the exact mechanism is largely unknown. Emerging studies have shown that the conversion into mesenchymal stem cells (MSCs) via the endothelial-to-mesenchymal transition (EndMT) could be trigger into adipocytes. In this study, we hypothesized whether CINA could attenuate bone loss in CKD rats by inhibition the endothelium to adipocytes transformation.

Methods

Eight-week male Sprague Dawley rats were divided into three groups: a control group (CTL), vehicle-treated CKD group (CKD) and a cinacalcet-treated CKD group (CKD+CINA). CKD was induced by a 0.75% adenine diet. After adenine withdrawal, all rats were maintained on high phosphate diets. We performed blood analysis, emission computed tomography (ECT), bone mechanical properties tests, dual energy X-ray absorptiometry (DEXA) and micro-computed tomography (micro-CT), bone histomorphometry assessments in rats at the age of 42 weeks. The bone marrow expression of EndMT- and adipocyte-markers were also examined.

Results

In CKD rats, CINA treatment significantly decreased the serum PTH, phosphate (P), and Ca (Calcium) × P product (P <0.05). The ECT images of the parathyroid glands indicated hyperparathyroidism in CKD rats but normal parathyroid function in CTL rats and CKD+CINA rats. Bone mineral density, trabecular BV/TV, trabecular number, cortical area, cortical thickness, force and stiffness were decreased in the CKD group, which were alleviated in the CKD+CINA group (P <0.05). The expression of endothelial marker (CD31) was significantly down-regulated in CKD rats, whereas the expression of mesenchymal marker (FSP1), mesenchymal stem cell markers (STRO-1, CD44, CD10), adipocyte-markers (PPAR-γ and LPL) were markedly up-regulated. These changes were inhibited by CINA treatment (P<0.05).

Conclusion

This study firstly demonstrated that CINA exerted a beneficial effect on bone loss in CKD through a novel mechanism of preventing bone marrow endothelial-to-adipocyte transition.

Funding

  • Clinical Revenue Support