穗花杉双黄酮通过阻断丝裂原活化蛋白激酶通路抑制钛颗粒诱导的骨溶解及破骨细胞的生成

Amentoflavone inhibits debris-induced osteolysis and osteoclastogenesis through blocking MAPK pathway

目的探讨中药单体穗花杉双黄酮(AMF)对钛颗粒诱导的小鼠颅骨骨溶解及RANKL诱导的破骨细胞的抑制作用及可能机制。方法构建骨溶解模型,随机分组:对照组;钛颗粒组;低、高浓度组。2周后行Micro-CT、HE、TRAP染色验证AMF对骨溶解的作用。CCK-8、TRAP染色及骨吸收实验验证AMF对破骨细胞生成及功能的影响;Western Blot检测AMF对MAPKs信号通路的影响。结果 Micro-CT及组织学分析示AMF能够抑制骨溶解及体内破骨细胞生成。CCK-8、TRAP染色及骨吸收实验示AMF(0、2.5、5、10μmol/L)能够抑制体外破骨细胞生成及功能并且无明显的毒性作用。Western Blot示AMF阻断了MAPK信号通路。结论 AMF抑制钛颗粒诱导的小鼠颅骨骨溶解及RANKL诱导的破骨细胞的生成可能是通过阻断MAPK通路起作用。

Objective To investigate the effect of amentoflavone （AMF） on inhibiting wear debris-in- duced osteolysis in vivo and RANKL-induced osteoclastogenesis in vitro. Methods Twenty-four male C57BL/J6 mice were randomly divided into four groups： the control group, titanium group, the low and high concentration group. Micro-CT and histological analysis were performed. CCK-8 assay was used to determin the effect of AMF on the proliferation of BblMs. TRAP staining and hone resorption assays were used to investigate the effect of AMF on osteoclastogenesis and function. The effect of AMF on prevention MAPK signaling was detected by Western blot assay. Results AMF could prevent osteolysis in vivo and suppress osteoclastogenesis, bone resorption without cytotoxicity in vitro. AMF suppressed MAPK signaling pathways. Conclusion AMF could inhibit osteoclastogenesis and titanium debris-induced osteolysis through suppressing MAPK signaling.