A rat model of SHPT with bone abnormalities in CKD induced by adenine and a high phosphorus diet

Ni, Lei; Tang, Ri‐Ning; Lv, Lin‐Li; Wu, Min; Wang, Bin; Wang, Fengmei; Ni, Haifeng; Song, Kun; Wang, Liting; Meng-Zuo,; Chen, Qiang; Liu, Bi‐Cheng

doi:10.1016/j.bbrc.2018.03.038

Cited by 14 publications

(13 citation statements)

References 39 publications

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“…Commonly used concentrations of phosphate in the diet are 1.2 [23] and 1.8% [24]. Recently, we developed a rat model of bone abnormalities in CKD induced by a diet containing adenine and 1.8% phosphate [20]. However, in our study and other studies, there was no obvious VC among rats fed a 1.8% phosphate diet, as shown by microcomputed tomography (micro-CT) examination [25].…”

Section: Introductionmentioning

confidence: 59%

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A Rat Model with Multivalve Calcification Induced by Subtotal Nephrectomy and High-Phosphorus Diet

et al. 2020

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Background: Chronic kidney disease (CKD) with known valve calcification (VC) places individuals at high risk of cardiovascular disease. The study of VC in CKD is challenging due to the lack of a suitable research model. Here, we established a rat model of multivalve calcification induced by subtotal nephrectomy and a high-phosphate (HP) diet and analyzed the valve characteristics. Methods: We established a CKD model in Sprague-Dawley rats by performing 5/6 nephrectomy (5/6Nx) followed by feeding with chow containing different phosphate concentrations for 8, 12, or 16 weeks. The rats were divided into 4 groups: sham+normal phosphate (NP, 0.9% P), sham+high phosphate (HP, 2.0% P), 5/6Nx+NP, and 5/6Nx+HP. Serum creatinine (Scr), blood This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

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Section: Introductionmentioning

confidence: 59%

“…Commonly used methods for CKD include surgery (5/6 nephrectomy, 5/6Nx) [18], electrocautery [19], and drug induction (adenine [20], oxalate [21]). The well-established 5/6Nx model used in our laboratory mimics human CKD with increased serum creatinine (Scr) levels [22] and tubulointerstitial fibrosis [18].…”

Section: Introductionmentioning

confidence: 99%

A Rat Model with Multivalve Calcification Induced by Subtotal Nephrectomy and High-Phosphorus Diet

et al. 2020

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“…In adenine-induced CKD model rats, Ni et al. [ 28 ] reported that the BMDs of femurs and lumbar vertebrae were significantly reduced, and the trabecular parameters including BV/TV, trabecular thickness, and trabecular number were decreased at 42 weeks after 4 weeks of feeding with 0.75% adenine and a high-phosphorus diet. Metzger et al.…”

Section: Discussionmentioning

confidence: 99%

Analysis of bone in adenine-induced chronic kidney disease model rats

Saito

Miyakoshi

Kasukawa

et al. 2021

Osteoporosis and Sarcopenia

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Objectives The purpose of this study is to investigate the stage of chronic kidney disease (CKD) in adenine-induced CKD model rats by serum analyses, and to examine bone mineral density (BMD), bone strength, and microstructure of trabecular and cortical bone in these rats. Methods Eight-week-old, male Wistar rats (n = 42) were divided into 2 groups: those fed a 0.75% adenine diet for 4 weeks until 12 weeks of age to generate CKD model rats (CKD group); and sham rats. The CKD and sham groups were sacrificed at 12, 16, and 20 weeks of age (n = 7 in each group and at 12, 16, and 20 weeks), and various parameters were evaluated, including body weight, renal wet weight, muscle wet weight, renal histology, biochemical tests, BMD, biomechanical testing, and micro-computed tomography (CT). The parameters were compared between the 2 groups at the various time points. Results In the CKD model rats, at 20 weeks of age, serum creatinine, phosphorus, and intact-PTH levels were elevated, and serum calcium levels were normal, indicating that the CKD was stage IV and associated with secondary hyperparathyroidism. Decreased BMDs of the whole body and the femur were observed as bone changes, and micro-CT analysis showed deterioration of bone microstructure of the cortical bone that resulted in decreased bone strength in the cortical and trabecular bone. Conclusions These CKD model rats showed stage IV CKD and appear appropriate for evaluating the effects of several treatments for CKD-related osteoporosis and mineral bone disorder.

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“…Ten animals were included in each group. Our rat models of CKD with SHPT were induced by diets containing 0.75% adenine and high phosphorus (1.5%), as previously described (28). CINA (Kirin Pharmaceutical Company, USA), a calcimimetic agent that has been widely used to reduce PTH secretion in patients with CKD, was orally administrated once daily (10 mg/kg) for 34 weeks (29).…”

Section: Animalsmentioning

confidence: 99%

Cinacalcet attenuated bone loss via inhibiting parathyroid hormone-induced endothelial-to-adipocyte transition in chronic kidney disease rats

Tang

Yuan

et al. 2019

Ann. Transl. Med.

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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 endothelialto-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 in vitro 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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A rat model of SHPT with bone abnormalities in CKD induced by adenine and a high phosphorus diet

Cited by 14 publications

References 39 publications

A Rat Model with Multivalve Calcification Induced by Subtotal Nephrectomy and High-Phosphorus Diet

A Rat Model with Multivalve Calcification Induced by Subtotal Nephrectomy and High-Phosphorus Diet

Analysis of bone in adenine-induced chronic kidney disease model rats

Cinacalcet attenuated bone loss via inhibiting parathyroid hormone-induced endothelial-to-adipocyte transition in chronic kidney disease rats

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