Asperosaponin VI protects against bone destructions in collagen induced arthritis by inhibiting osteoclastogenesis
Asperosaponin VI protects against bone destructions in collagen induced arthritis by inhibiting osteoclastogenesis
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Asperosaponin VI 通过抑制破骨细胞生成来防止胶原诱导的关节炎中的骨质破坏
DOI：
10.1016/j.phymed.2019.153006
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发表时间：
2019-10-01
期刊：
影响因子：
7.9
通讯作者：
Zhou, Chun
中科院分区：
文献类型：
--
作者：
Liu, Kaifei;Liu, Ying;Zhou, Chun
背景：类风湿性关节炎（RA）、骨质疏松症和骨转移瘤等骨破坏性疾病主要是由过度活化的破骨细胞介导的。 Asperosaponin VI (AVI) 是从续断根茎中分离得到的三萜皂苷类化合物。它具有多种生理活性，但其对RA的影响，特别是对破骨细胞分化和活化的影响尚不清楚。目的：探讨AVI对体内胶原诱导关节炎（CIA）和体外RANKL诱导破骨细胞生成的保护作用。方法：使用骨髓来源的单核细胞测试AVI对细胞活力和RANKL诱导的破骨细胞生成、肌动蛋白环形成、骨吸收活性以及对破骨细胞特异性基因和蛋白表达的影响（BMM）。使用 CIA 小鼠的爪子进行显微 CT、HE 和 TRAP 染色、实时 PCR 和蛋白质印迹。使用血清通过ELISA进行细胞因子分析。采用蛋白质印迹、实时PCR和免疫荧光检测信号通路。结果：AVI通过抑制肌动蛋白环的形成，显着抑制RANKL诱导的破骨细胞形成和骨吸收活性。它还抑制多种破骨细胞标志基因和信号通路的表达。 AVI通过抑制炎症和骨质流失来保护体内关节炎。结论：AVI通过抑制RANKL诱导的破骨细胞分化和功能在体外和体内发挥其抗破骨细胞生成活性。因此，我们的研究证明了 AVI 在预防或抑制 RANKL 介导的溶骨性骨疾病方面具有潜在的治疗作用。
Background: Bone destructive diseases like rheumatoid arthritis (RA), osteoporosis and bone metastatic tumors are mainly mediated by over-activated osteoclasts. Asperosaponin VI (AVI), isolated from the rhizome of Dipsacus asper, belongs to triterpenoid saponins. It has multiple physiological activities but its effects on RA, especially on osteoclast differentiation and activation are still unclear.Purpose: Explore the protective role of AVI on collagen induced arthritis (CIA) in vivo and RANKL induced osteoclastogenesis in vitro.Methods: The effects of AVI on cell viability and RANKL-induced osteoclastogenesis, actin ring formation, bone resorption activity as well as on osteoclast specific gene and protein expression were tested using bone marrow derived monocytes (BMMs). Paws from CIA mice were used for micro-CT, HE and TRAP staining, real-time PCR and western blot. Sera were used for cytokine analysis by ELISA. The signaling pathways were detected using western blot, real-time PCR and immunofluorescence assay.Results: AVI significantly inhibited RANKL-induced osteoclast formation and bone resorption activity by suppressing the formation of actin ring. It also inhibited the expression of various osteoclatogenesis marker genes and signaling pathways. AVI protected arthritis in vivo by suppressing inflammation and bone loss.Conclusion: AVI exerts its anti-osteoclastogenic activity both in vitro and in vivo by inhibiting RANKL-induced osteoclast differentiation and function. Thus, our studies demonstrate a potential therapeutic role for AVI in preventing or inhibiting RANKL-mediated osteolytic bone diseases.