Cinacalcet Attenuated Bone Loss Via Inhibiting Parathyroid Hormone-induced Endothelial-to-adipocyte Transition in Chronic Kidney Disease Rats

Overview

Journal Ann Transl Med

Publisher AME Publishing Company

Date 2019 Sep 3

PMID 31475182

Citations 4

Authors

Li-Hua Ni

Ri-Ning Tang

Cheng Yuan

Kai-Yun Song

Li-Ting Wang

Xiao-Liang Zhang

Lin-Li Lv

Bin Wang

Min Wu

Tao-Tao Tang

Zuo-Lin Li

Di Yin

Jing-Yuan Cao

Xiao-Chen Wang

Hong Liu

Qiang Chen

Bi-Cheng Liu

Affiliations

Soon will be listed here.

Abstract

Background: Recently, cinacalcet (CINA) has been shown to be effective for attenuating bone loss in the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD), which might be associated with the reduction in serum parathyroid hormone (PTH) levels. However, the exact mechanism is largely unclear. Emerging studies have revealed that an increased number of bone marrow adipocytes (BMAs) are involved in bone loss and the endothelial-to-adipocyte transition via the endothelial-to-mesenchymal transition (EndMT) might play a key role in this pathological process. Here, we assessed whether CINA could attenuate bone loss via inhibiting endothelial-to-adipocyte transition in CKD rats.

Methods: A rat model of CKD was induced by adenine and a high phosphorus diet. CINA was orally administrated to CKD animals (10 mg/kg once a day). Dual energy X-ray absorptiometry, micro-computed tomography, bone histomorphometry, and bone mechanical tests were used to determine the skeletal changes. The bone marrow expression of EndMT markers was also examined. The effect of elevated PTH levels on the endothelial-to-adipocyte transition was studied in endothelial cells (ECs).

Results: Elevation of serum PTH levels, remarkable bone loss and increased numbers of BMAs were observed in rats with CKD compared with the controls, and these changes were attenuated after treatment with CINA. Furthermore, the CINA treatment abolished the upregulation of mesenchymal markers (FSP1 and α-SMA) and the downregulation of an endothelial marker (CD31) in bone tissues from rats with CKD. The serum PTH concentrations were correlated with the bone marrow protein levels of these EndMT-related proteins. An treatment in ECs demonstrated that PTH induced the EndMT in a concentration- and time-dependent manner. Accordingly, ECs treated with PTH exhibited adipogenic potential following growth in adipogenic culture medium.

Conclusions: Our study indicated CINA treatment attenuated bone loss in CKD rats, which might be associated with inhibiting PTH-induced endothelial-to-adipocyte transition in CKD rats.

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