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      Recent Progresses in the Treatment of Osteoporosis

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          Abstract

          Osteoporosis (OP) is a chronic bone disease characterized by aberrant microstructure and macrostructure of bone, leading to reduced bone mass and increased risk of fragile fractures. Anti-resorptive drugs, especially, bisphosphonates, are currently the treatment of choice in most developing countries. However, they do have limitations and adverse effects, which, to some extent, helped the development of anabolic drugs such as teriparatide and romosozumab. In patients with high or very high risk for fracture, sequential or combined therapies may be considered with the initial drugs being anabolic agents. Great endeavors have been made to find next generation drugs with maximal efficacy and minimal toxicity, and improved understanding of the role of different signaling pathways and their crosstalk in the pathogenesis of OP may help achieve this goal. Our review focused on recent progress with regards to the drug development by modification of Wnt pathway, while other pathways/molecules were also discussed briefly. In addition, new observations made in recent years in bone biology were summarized and discussed for the treatment of OP.

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          Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities.

          The WNT signal transduction cascade is a main regulator of development throughout the animal kingdom. Wnts are also key drivers of most types of tissue stem cells in adult mammals. Unsurprisingly, mutated Wnt pathway components are causative to multiple growth-related pathologies and to cancer. Here, we describe the core Wnt/β-catenin signaling pathway, how it controls stem cells, and contributes to disease. Finally, we discuss strategies for Wnt-based therapies.
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            Wnt/β-catenin signaling and disease.

            The WNT signal transduction cascade controls myriad biological phenomena throughout development and adult life of all animals. In parallel, aberrant Wnt signaling underlies a wide range of pathologies in humans. In this Review, we provide an update of the core Wnt/β-catenin signaling pathway, discuss how its various components contribute to disease, and pose outstanding questions to be addressed in the future. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Wnt/beta-catenin signaling: components, mechanisms, and diseases.

              Signaling by the Wnt family of secreted glycolipoproteins via the transcriptional coactivator beta-catenin controls embryonic development and adult homeostasis. Here we review recent progress in this so-called canonical Wnt signaling pathway. We discuss Wnt ligands, agonists, and antagonists, and their interactions with Wnt receptors. We also dissect critical events that regulate beta-catenin stability, from Wnt receptors to the cytoplasmic beta-catenin destruction complex, and nuclear machinery that mediates beta-catenin-dependent transcription. Finally, we highlight some key aspects of Wnt/beta-catenin signaling in human diseases including congenital malformations, cancer, and osteoporosis, and discuss potential therapeutic implications.
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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
                22 July 2021
                2021
                : 12
                : 717065
                Affiliations
                [ 1 ]Department of Rheumatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
                [ 2 ]Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
                [ 3 ]Department of Magnetic Resonance Imaging, Henan Key Laboratory of Functional Magnetic Resonance Imaging and Molecular Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
                Author notes

                Edited by: Liangliang Xu, Guangzhou University of Chinese Medicine, China

                Reviewed by: Bin Wang, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, China

                Daohua Xu, Guangdong Medical University, China

                Xianzuo Zhang, Anhui Provincial Hospital, China

                *Correspondence: Tian-Fang Li, tfli@ 123456zzu.edu.cn ; Dai-Feng Li, lidaifeng_ldf@ 123456163.com

                This article was submitted to Integrative and Regenerative Pharmacology, a section of the journal Frontiers in Pharmacology

                Article
                717065
                10.3389/fphar.2021.717065
                8339209
                34366868
                34c78fde-67eb-4394-82ee-d50ae5b83ef4
                Copyright © 2021 Li, He, Xie, Li, Zhang, Li and Li.

                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
                : 30 May 2021
                : 12 July 2021
                Funding
                Funded by: National Natural Science Foundation of China-Henan Joint Fund 10.13039/501100014220
                Award ID: U1704177 81871811
                Funded by: China Postdoctoral Science Foundation 10.13039/501100002858
                Award ID: 2020TQ0281
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                osteoporosis,antiresorptive drugs,anabolic drugs,wnt signaling pathway,bone formation

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