کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8628929 | 1568706 | 2018 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
RANKL/OPG system regulation by endogenous PTH and PTH1R/ATF4 axis in bone: Implications for bone accrual and strength in growing rats with mild uremia
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کلمات کلیدی
ATF4RANKLpTHOPGvBMDreceptor activator of nuclear factor kappa-BPTH1ROsteoprotegerin - استئوپروتگرینchronic kidney disease - بیماری مزمن کلیویvolumetric bone mineral density - تراکم معدنی استخوانی حجمیRank - رتبهactivating transcription factor 4 - فعال کردن عامل رونویسی 4Growing rats - موش های در حال رشدCKD - نارسایی مزمن کلیهparathyroid hormone - هورمون پاراتیروئید
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
علوم غدد
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), and parathyroid hormone (PTH) play a central role in the regulation of bone turnover in chronic kidney disease (CKD), but their influence on bone mineral density (BMD) and strength remains unclear, particularly in children. We studied the clinical significance of OPG and RANKL in relation to PTH, femur weight, BMD, and bone biomechanical properties in growing rats after one month (CKD-1) and three months (CKD-3) of surgically-induced mild CKD. Gene expression of parathyroid hormone 1 receptor (PTH1R) and activating transcription factor 4 (ATF4), major regulators of anabolic PTH response in bone, was also determined. Serum PTH and bone PTH1R/ATF4 expression was elevated in CKD-3 compared with other groups, and it positively correlated with femur weight, BMD, and the biomechanical properties of the femoral diaphysis reflecting cortical bone strength. In contrast, bone RANKL/OPG ratios were decreased in CKD-3 rats compared with other groups, and they were inversely correlated with PTH and the other abovementioned bone parameters. However, the PTH-PTH1R-ATF4 axis exerted an unfavorable effect on the biomechanical properties of the femoral neck. In conclusion, this study showed for the first time an inverse association between serum PTH and the bone RANKL/OPG system in growing rats with mild CKD. A decrease in the RANKL/OPG ratio, associated with PTH-dependent activation of the anabolic PTH1R/ATF4 pathway, seems to be responsible for the unexpected, beneficial effect of PTH on cortical bone accrual and strength. Simultaneously, impaired biomechanical properties of the femoral neck were observed, making this bone site more susceptible to fractures.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cytokine - Volume 106, June 2018, Pages 19-28
Journal: Cytokine - Volume 106, June 2018, Pages 19-28
نویسندگان
Beata Znorko, Dariusz Pawlak, Ewa Oksztulska-Kolanek, Tomasz Domaniewski, Anna Pryczynicz, Alicja Roszczenko, Joanna Rogalska, PaweÅ Lipowicz, MichaÅ Doroszko, Malgorzata Michalina Brzoska, Krystyna Pawlak,