Wang Lu, Chen Kai, He Jianbo, Kenny Jacob, Yuan Yu, Chen Junhao, Liu Qian, Tan Renxiang, Zhao Jinmin, Xu Jiake
Department of Orthopaedics, The First Affiliated Hospital of Wenzhou Medical University Zhejiang Province China.
School of Biomedical Sciences, University of Western Australia Perth 6009 WA Australia
RSC Adv. 2019 Nov 25;9(66):38438-38446. doi: 10.1039/c9ra07240c.
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 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 , , and . 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.
破骨细胞生成过多和骨吸收增强是包括溶骨性疾病、骨质疏松症和关节炎在内的骨疾病的病理特征。针对高度活化破骨细胞的治疗被认为是治疗破骨细胞相关骨疾病的有前景的疗法。细胞松弛素是已知的真菌次生代谢产物，在细胞生物学和医学中表现出多种生物活性。细胞松弛素Z11（CytoZ11）先前通过固体基质培养从[来源未明确]中分离出来，并显示出对白血病的治疗潜力。然而，CytoZ11对破骨细胞的作用目前仍不清楚。在此，发现CytoZ11能够剂量依赖性地减弱核因子κB受体激活剂配体（RANKL）诱导的破骨细胞生成和骨吸收活性。CytoZ11还能抑制破骨细胞特异性基因如[基因名称未明确]、[基因名称未明确]和[基因名称未明确]的mRNA表达。此外，CytoZ11被证明可抑制NFATc1激活，这是由于两条信号通路的减弱：c-Fos信号通路和NF-κB通路。总之，本研究表明CytoZ11可能通过抑制破骨细胞形成和功能而成为破骨细胞相关疾病的一种有前景的药物。
