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Sarsasapogenin Suppresses RANKL-Induced Osteoclastogenesis in vitro and Prevents Lipopolysaccharide-Induced Bone Loss in vivo.
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-08-24 , DOI: 10.2147/dddt.s256867
Jiaxuan Peng 1 , Kangxian Zhao 2 , Jiling Zhu 3 , Yanben Wang 4, 5 , Peng Sun 2 , Qichang Yang 2 , Tan Zhang 4 , Weiqi Han 4 , Wenjun Hu 4 , Wanlei Yang 4 , Jianwei Ruan 6 , Yu Qian 1, 2, 4
Affiliation  

Introduction: Osteoclasts are giant polynuclear cells; their main function is bone resorption. An increased number of osteoclasts and enhanced bone resorption exert significant effects on osteoclast-related bone-lytic diseases, including osteoporosis. Given the limitations of current therapies for osteolytic diseases, it is urgently required to develop safer and more effective alternatives. Sarsasapogenin, a major sapogenin from Anemarrhena asphodeloides Bunge, possesses potent antitumor effects and inhibits NF-κB and MAPK signaling. However, the manner in which it affects osteoclasts is unclear.
Methods: We investigated the effects of anti-osteoclastogenic and anti-resorptive of sarsasapogenin on bone marrow-derived osteoclasts.
Results: Sarsasapogenin inhibited multiple RANKL-induced signaling cascades, thereby inhibiting the induction of key osteoclast transcription factor NFATc1. The in vivo and in vitro results were consistent: sarsasapogenin treatment protected against bone loss in a mouse osteolysis model induced by lipopolysaccharide.
Conclusion: Our research confirms that sarsasapogenin can be used as a new treatment for osteoclast-related osteolytic diseases.

Keywords: sarsasapogenin, osteoclast, osteoclastogenesis, NF-κB, MAPK, NFATc1, therapeutics


中文翻译:

Sarsasapogenin 在体外抑制 RANKL 诱导的破骨细胞生成,并在体内防止脂多糖诱导的骨丢失。

简介:破骨细胞是巨大的多核细胞;它们的主要功能是骨吸收。破骨细胞数量的增加和骨吸收的增强对破骨细胞相关的溶骨性疾病(包括骨质疏松症)产生显着影响。鉴于目前溶骨性疾病疗法的局限性,迫切需要开发更安全、更有效的替代方案。Sarsasapogenin 是知母中的一种主要皂苷元具有有效的抗肿瘤作用并抑制 NF-κB 和 MAPK 信号传导。然而,它影响破骨细胞的方式尚不清楚。
方法:我们研究了萨洒皂草配基的抗破骨细胞生成和抗吸收作用对骨髓源性破骨细胞的影响。
结果: Sarsasapogenin 抑制多个 RANKL 诱导的信号级联反应,从而抑制关键破骨细胞转录因子 NFATc1 的诱导。体内和体外结果是一致的:萨洒皂草配基治疗可防止脂多糖诱导的小鼠骨质溶解模型中的骨质流失。
结论:我们的研究证实萨洒皂草配基可以作为破骨细胞相关溶骨性疾病的新治疗方法。

关键词:萨洒皂草配基, 破骨细胞, 破骨细胞生成, NF-κB, MAPK, NFATc1, 治疗
更新日期:2020-08-24
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