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Cytochalasin Z11 inhibits RANKL-induced osteoclastogenesis: Via suppressing NFATc1 activation(Open Access)

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机构： [1]Departmentof Orthopaedics, The First Affiliated Hospital of Wenzhou MedicalUniversity, Zhejiang Province, China [2]School of Biomedical Sciences, University of Western Australia, Perth 6009, WA,Australia [3]Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China [4]School of Physical Education and Sports Science, South China Normal University,Guangzhou, Guangdong, China [5]Research Centre for Regenerative Medicine, Guangxi Medical University, GuangxiProvince, China [6]Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University,Guangxi, China [7]International Joint Laboratory on Regeneration of Bone and So Tissues, GuangxiMedical University, Guangxi, China [8]The State Key Laboratory of Pharmaceutical Biotechnology, Institute of FunctionalBiomolecules, Nanjing University, Nanjing, China

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Excessive osteoclastogenesis and enhanced bone resorption are pathological hallmarks for bone diseases including osteolytic diseases, osteoporosis, and arthritis. Treatments targeting highly activated osteoclasts are regarded as promising therapies for osteoclast-related bone disorders. Cytochalasins are known as secondary metabolites of fungi and exhibit a variety of biological activities in cell biology and medicine. Cytochalasin Z11 (CytoZ11) was previously isolated from the Endothia gyrosa through solid substrate culture and showed therapeutic potential for leukaemia. However, the effects of CytoZ11 on osteoclasts currently remain unclear. Herein, CytoZ11 was found to be able to attenuate RANKL (receptor activator of nuclear factor-κB ligand)-induced osteoclastogenesis and bone resorptive activity dose-dependently. CytoZ11 could also inhibit mRNA expression of osteoclast-specific genes such as Ctr, Acp5, and Ctsk. Furthermore, CytoZ11 was demonstrated to suppress NFATc1 activation, which is due to the attenuation of two signaling pathways: c-Fos signaling and the NF-κB pathway. In summary, this study revealed that CytoZ11 may become a prospective drug for osteoclast-related disease by inhibiting osteoclast formation and function. © 2019 The Royal Society of Chemistry.

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出版当年[2018]版：

大类 | 3 区化学

小类 | 3 区化学综合

最新[2025]版：

大类 | 3 区化学

小类 | 3 区化学：综合

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第一作者机构： [1]Departmentof Orthopaedics, The First Affiliated Hospital of Wenzhou MedicalUniversity, Zhejiang Province, China

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