Cinacalcet Improves Bone Parameters Through Regulation of Osteoclast Endoplasmic Reticulum Stress, Autophagy, and Apoptotic Pathways in Chronic Kidney Disease–Mineral and Bone Disorder
| العنوان: | Cinacalcet Improves Bone Parameters Through Regulation of Osteoclast Endoplasmic Reticulum Stress, Autophagy, and Apoptotic Pathways in Chronic Kidney Disease–Mineral and Bone Disorder |
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| المؤلفون: | Chien-Lin Lu, Cai Mei Zheng, Jia-Feng Chang, Kuo-Cheng Lu, Jia Fwu Shyu, Wen-Chih Liu, Yi-Chou Hou, Hui-Wen Chiu |
| المصدر: | Journal of Bone and Mineral Research. 37:215-225 |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | medicine.medical_specialty, Cinacalcet, Endocrinology, Diabetes and Metabolism, Osteoclasts, Mice, Osteoclast, Chronic kidney disease-mineral and bone disorder, Internal medicine, Autophagy, medicine, Animals, Orthopedics and Sports Medicine, Protein kinase B, PI3K/AKT/mTOR pathway, Chronic Kidney Disease-Mineral and Bone Disorder, biology, Chemistry, RANK Ligand, Cell Differentiation, X-Ray Microtomography, Endoplasmic Reticulum Stress, medicine.disease, medicine.anatomical_structure, Endocrinology, RANKL, biology.protein, Unfolded protein response, medicine.drug |
| الوصف: | The possible mechanisms underlying the quantitative and qualitative effects of cinacalcet on bone were explored in a chronic kidney disease-mineral and bone disorder (CKD-MBD) mouse model in relation to the influence of the interactions among the osteoclast (OC) endoplasmic reticulum (ER) stress, autophagy and apoptosis pathways on OC differentiation. Body weight and biochemical parameters improved significantly in the CKD + cinacalcet groups compared to the CKD group. Micro-computed tomography (μCT) revealed both cortical and trabecular parameters deteriorated significantly in the CKD group and were reversed by cinacalcet in a dose-dependent manner. Nanoindentation analysis of bone quality proved that both cortical hardness and elastic modulus improved significantly with high dose cinacalcet treatment. In vitro studies revealed that cinacalcet inhibited receptor activator of NF-κB ligand (RANKL)/receptor activator of NF-κB (RANK)-induced OC differentiation in a concentration-dependent manner through a close interaction between activation of caspase-related apoptosis, reversal of OC autophagy through the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK) pathways, and attenuation of the OC ER stress/CREBH/NFATc1 signaling pathway. Cinacalcet improves both bone quantity and bone quality in CKD mouse model and inhibits OC differentiation through regulation of the interactions among the apoptosis, ER stress, and autophagy pathways within OCs. © 2021 American Society for Bone and Mineral Research (ASBMR). |
| تدمد: | 1523-4681 0884-0431 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::815eb9d8fadf88be98fe9951571dcff1Test https://doi.org/10.1002/jbmr.4459Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....815eb9d8fadf88be98fe9951571dcff1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15234681 08840431 |
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