Department of Orthopedics, The First Affiliated Hospital of Soochow University, PR China.
Department of Orthopedics, The First Affiliated Hospital of Soochow University, PR China; Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, PR China.
Biomaterials. 2015 Aug;60:92-9. doi: 10.1016/j.biomaterials.2015.04.048. Epub 2015 May 15.
Periprosthetic osteolysis and subsequent aseptic loosening are common in implant failure, a complication with revision surgery being the only established treatment. Wear particle-induced inflammation and extensive osteoclastogenesis play critical roles in periprosthetic osteolysis. A recent approach in limiting osteolysis is therefore focused on inhibiting osteoclastic bone resorption. This study aimed to investigate the potential impact of icariin, the major ingredient of Epimedium, on titanium particle-induced osteolysis in a mouse calvarial model. Eighty-four male C57BL/J6 mice were divided randomly into four groups. Mice in the sham group underwent sham surgery only, whereas animals in the vehicle, low- and high-concentration icariin groups received titanium particles. Mice in the low- and high-concentration icariin groups were gavage-fed with icariin at 0.1 or 0.3 mg/g/day, respectively, until sacrifice. Mice in the sham and vehicle groups received phosphate-buffered saline daily. After 2 weeks, mouse calvariae were collected for micro-computed tomography, histomorphometry and molecular analysis. Icariin significantly reduced particle-induced bone resorption compared with the vehicle group. Icariin also prevented an increase in receptor activator of nuclear factor kappa B ligand/osteoprotegerin ratio and subsequently suppressed osteoclast formation in titanium particle-charged calvariae. In addition, immunohistochemical analysis and enzyme-linked immunosorbent assay showed icariin significantly reduced expression and secretion of tumor necrosis factor-α, interleukin-1β and interleukin-6 in the calvariae of titanium-stimulated mice. Collectively, these results suggest that icariin represents a potential treatment for titanium particle-induced osteolysis and could be developed as a new therapeutic candidate for the prevention and treatment of aseptic loosening.
假体周围骨溶解和随后的无菌性松动是植入物失败的常见并发症，翻修手术是唯一确定的治疗方法。磨屑诱导的炎症和广泛的破骨细胞生成在假体周围骨溶解中起着关键作用。因此，限制骨溶解的一种新方法是专注于抑制破骨细胞的骨吸收。本研究旨在探讨淫羊藿素（淫羊藿的主要成分）在小鼠颅骨模型中对钛颗粒诱导的骨溶解的潜在影响。84 只雄性 C57BL/J6 小鼠被随机分为四组。假手术组仅接受假手术，而载体组、低浓度淫羊藿素组和高浓度淫羊藿素组的动物接受钛颗粒。低浓度和高浓度淫羊藿素组的小鼠分别以 0.1 或 0.3mg/g/天的剂量灌胃淫羊藿素，直到处死。假手术组和载体组的小鼠每天接受磷酸盐缓冲液。2 周后，收集小鼠颅骨进行微计算机断层扫描、组织形态计量学和分子分析。与载体组相比，淫羊藿素显著减少了颗粒诱导的骨吸收。淫羊藿素还防止了核因子 kappa B 配体/骨保护素受体比率的增加，并随后抑制了钛颗粒负荷颅骨中的破骨细胞形成。此外，免疫组织化学分析和酶联免疫吸附试验显示，淫羊藿素显著降低了钛刺激小鼠颅骨中肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6 的表达和分泌。总之，这些结果表明淫羊藿素是一种治疗钛颗粒诱导的骨溶解的潜在药物，可作为预防和治疗无菌性松动的新治疗候选药物。
