Xiao Fei, Zhai Zanjing, Jiang Chuan, Liu Xuqiang, Li Haowei, Qu Xinhua, Ouyang Zhengxiao, Fan Qiming, Tang Tingting, Qin An, Gu Dongyun
Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People׳s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People׳s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China; Department of Orthopaedics, Hunan Provincial Tumor Hospital and Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, PR China.
Exp Cell Res. 2015 Jan 1;330(1):91-101. doi: 10.1016/j.yexcr.2014.07.005. Epub 2014 Jul 9.
Wear particle-induced osteolysis and subsequent aseptic loosening remains the most common complication that limits the longevity of prostheses. Wear particle-induced osteoclastogenesis is known to be responsible for extensive bone erosion that leads to prosthesis failure. Thus, inhibition of osteoclastic bone resorption may serve as a therapeutic strategy for the treatment of wear particle induced osteolysis. In this study, we demonstrated for the first time that geraniin, an active natural compound derived from Geranium thunbergii, ameliorated particle-induced osteolysis in a Ti particle-induced mouse calvaria model in vivo. We also investigated the mechanism by which geraniin exerts inhibitory effects on osteoclasts. Geraniin inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, evidenced by reduced osteoclast formation and suppressed osteoclast specific gene expression. Specially, geraniin inhibited actin ring formation and bone resorption in vitro. Further molecular investigation demonstrated geraniin impaired osteoclast differentiation via the inhibition of the RANKL-induced NF-κB and ERK signaling pathways, as well as suppressed the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Collectively, our data suggested that geraniin exerts inhibitory effects on osteoclast differentiation in vitro and suppresses Ti particle-induced osteolysis in vivo. Geraniin is therefore a potential natural compound for the treatment of wear particle induced osteolysis in prostheses failure.
磨损颗粒诱导的骨溶解及随后的无菌性松动仍然是限制假体使用寿命的最常见并发症。已知磨损颗粒诱导破骨细胞生成是导致广泛骨侵蚀并最终导致假体失效的原因。因此，抑制破骨细胞介导的骨吸收可能是治疗磨损颗粒诱导的骨溶解的一种治疗策略。在本研究中，我们首次证明了老鹳草素（一种从日本老鹳草中提取的活性天然化合物）在体内钛颗粒诱导的小鼠颅骨模型中可改善颗粒诱导的骨溶解。我们还研究了老鹳草素对破骨细胞发挥抑制作用的机制。老鹳草素以剂量依赖的方式抑制RANKL诱导的破骨细胞生成，表现为破骨细胞形成减少和破骨细胞特异性基因表达受到抑制。特别地，老鹳草素在体外抑制肌动蛋白环形成和骨吸收。进一步的分子研究表明，老鹳草素通过抑制RANKL诱导的NF-κB和ERK信号通路来损害破骨细胞分化，并抑制关键破骨细胞转录因子NFATc1和c-Fos的表达。总体而言，我们的数据表明老鹳草素在体外对破骨细胞分化具有抑制作用，并在体内抑制钛颗粒诱导的骨溶解。因此，老鹳草素是一种治疗假体失效中磨损颗粒诱导的骨溶解的潜在天然化合物。
