槐黄烷酮G抑制破骨细胞分化和减少骨丢失的机制研究
Sophoraflavanone G inhibits RANKL-induced osteoclastogenesis and alleviates bone loss
王民政 1李泳瑜 2刘为雯 2张诗茵 2梁梓炫 2陈思敏 2郑泉鑫 3黄立宇 3钟露斌 4江政晃 5汤凯6
作者信息
- 1. 江西中医药大学附属医院,江西 南昌 330006
- 2. 广州中医药大学,广东 广州 510405
- 3. 广州市正骨医院,广东 广州 510055
- 4. 广州粤海医院,广东 广州 510430
- 5. 龙川县人民医院,广东 河源 517399
- 6. 广州中医药大学,广东 广州 510405;广州中医药大学第一附属医院,广东 广州 510405
- 折叠
摘要
目的 通过体内与体外实验相结合探讨槐黄烷酮G抑制破骨细胞形成和分化,从而缓解骨丢失现象的作用机制研究.方法 通过CCK-8和TRAcP染色实验验证槐黄烷酮G是否具有抑制破骨细胞形成的作用;通过分子对接验证槐黄烷酮G与破骨细胞分化相关的特异性蛋白结合的亲和力大小,借助RT-PCR和Western blot实验探讨槐黄烷酮G抑制破骨细胞形成的作用机制;最后通过体内实验进一步探讨,以验证体外实验的准确性和可靠性.结果 槐黄烷酮G能够在安全浓度下抑制破骨细胞形成和分化,同时也与破骨细胞相关的特异性蛋白如NFATc1、CTSK、c-Fos、MMP9 具有较高的亲和力,并能够降低上述基因和蛋白的相对表达水平,槐黄烷酮G也能够在 15 和 30 min处有效降低MAPK信号通路中的ERK和JNK的磷酸化表达水平,体内实验证明槐黄烷酮G能够起到缓解骨丢失,改善骨小梁相关参数的作用.结论 槐黄烷酮G具有抑制破骨细胞形成和分化,缓解骨量减少的作用,从而起到抗骨质疏松症的作用.
Abstract
Objective To investigate the mechanism of Sophoraflavanone G in inhibiting osteoclast formation and differentiation,thereby alleviating bone loss,through a combination of in vivo and in vitro experiments.Methods The inhibitory effect of Sophoraflavanone G on osteoclast formation was verified with CCK-8 and TRAcP staining experiments.The affinity of Sophoraflavanone G binding to specific proteins related to osteoclast differentiation was validated with molecular docking.The mechanism of Sophoraflavanone G inhibition of osteoclast formation was explored using RT-PCR and Western blotting experiments.Finally,in vivo experiments were conducted to verify the accuracy and reliability of the in vitro experiments.Results Sophoraflavanone G inhibited the formation and differentiation of osteoclasts at safe concentrations.It had a high affinity with osteoclast-related specific proteins such as NFATc1,CTSK,c-Fos,and MMP9.It reduced the relative expression levels of these genes and proteins.Sophoraflavanone G effectively reduced the phosphorylation expression levels of ERK and JNK in the MAPK signaling pathway at 15 and 30 minutes.In vivo experiments showed that Sophoraflavanone G alleviated bone loss and improved trabecular related parameters.Conclusion Sophoraflavanone G has the ability to inhibit the formation and differentiation of osteoclasts,to alleviate bone loss,thereby playing a role in combating osteoporosis.
关键词
骨质疏松/破骨细胞/苦参/骨碎补/槐黄烷酮GKey words
osteoporosis/osteoclasts/Alt Rhizoma/drynariae/sophoraflavanone G引用本文复制引用
基金项目
江西中医药管理局科技计划项目(2022A240)
广州中医药大学大学生创新创业训练计划项目(202210572184)
出版年
2024