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      Corydalis Saxicola Bunting Total Alkaloids Attenuate Walker 256-Induced Bone Pain and Osteoclastogenesis by Suppressing RANKL-Induced NF-κB and c-Fos/NFATc1 Pathways in Rats

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          Abstract

          Metastatic bone pain is characterized by insufferable bone pain and abnormal bone structure. A major goal of bone cancer treatment is to ameliorate osteolytic lesion induced by tumor cells. Corydalis saxicola Bunting total alkaloids (CSBTA), the alkaloid compounds extracted from the root of C. saxicola Bunting, have been shown to possess anticancer and analgesic properties . In this study, we aimed to verify whether CSBTA could relieve cancer induced bone pain and inhibit osteoclastogenesis. The in vivo results showed that CSBTA ameliorated Walker 256 induced bone pain and osteoporosis in rats. Histopathological changes also supported that CSBTA inhibited Walker 256 cell-mediated osteolysis. Further in vitro analysis confirmed that CSBTA reduced the expression of RANKL and downregulate the level of RANKL/OPG ratio in breast cancer cells. Moreover, CSBTA could inhibit osteoclastogenesis by suppressing RANKL-induced NF-κB and c-Fos/NFATc1 pathways. Collectively, this study demonstrated that CSBTA could attenuate cancer induced bone pain via a novel mechanism. Therefore, CSBTA might be a promising candidate drug for metastatic bone pain patients.

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              Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab.

              Bone is a complex tissue that provides mechanical support for muscles and joints, protection for vital organs, a mineral reservoir that is essential for calcium homeostasis, and the environment and niches required for haematopoiesis. The regulation of bone mass in mammals is governed by a complex interplay between bone-forming cells termed osteoblasts and bone-resorbing cells termed osteoclasts, and is guided physiologically by a diverse set of hormones, cytokines and growth factors. The balance between these processes changes over time, causing an elevated risk of fractures with age. Osteoclasts may also be activated in the cancer setting, leading to bone pain, fracture, spinal cord compression and other significant morbidities. This Review chronicles the events that led to an increased understanding of bone resorption, the elucidation of the signalling pathway mediated by osteoprotegerin, receptor activator of NF-κB (RANK) and RANK ligand (RANKL) and its role in osteoclast biology, as well as the evolution of recombinant RANKL antagonists, which culminated in the development of the therapeutic RANKL-targeted antibody denosumab.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                26 January 2021
                2020
                : 11
                : 609119
                Affiliations
                [ 1 ]Department of Chinese Pharmacology and Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, China
                [ 2 ]Nanjing Zhongshan Pharmaceutical Co, Ltd., Nanjing Economic and Technological Development Zone, Nanjing, China
                Author notes

                Edited by: Vincent Kam Wai Wong, Macau University of Science and Technology, Macau

                Reviewed by: Linna Wang, Macau University of Science and Technology, Macau

                Jiacan Su, Second Military Medical University, China

                *Correspondence: Jun Cheng, huangfangcpuzyxy@ 123456163.com ; Fang Huang, huangfang@ 123456cpu.edu.cn

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                609119
                10.3389/fphar.2020.609119
                7870471
                33574755
                c7aaacf7-ff78-4847-9d33-22974b3c6790
                Copyright © 2021 Ju, Hu, Chen, Wu, Li, Qiu, Cheng and Huang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 22 September 2020
                : 17 December 2020
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                corydalis saxicola bunting total alkaloids,cancer induced bone pain,osteoclastogenesis,iκbα,rankl induced nf-κb and c-fos/nfatc1 pathways

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