Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, The People's Republic of China.
Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, The People's Republic of China.
Biochem Pharmacol. 2015 Jan 1;93(1):59-71. doi: 10.1016/j.bcp.2014.10.019. Epub 2014 Nov 7.
Titanium (Ti) particle-induced periprosthetic osteolysis and subsequent aseptic loosening are a primary reason for total hip arthroplasty failure. The aim of this study was to assess the effect of myricetin on Ti particle-induced osteolysis and osteoclastogenesis. We demonstrated that myricetin, a natural plant extract, exerts potent inhibitory effects on Ti particle-induced osteolysis in a mouse calvarial model. Further histological analysis indicated that the inhibition of osteoclast formation and function, and the secretion of inflammatory factors, are key targets for therapeutic agents in the treatment of wear particle-induced osteolysis. In vitro, we found that myricetin suppressed receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclast differentiation, bone resorption, and F-actin ring formation in a dose-dependent manner. Moreover, myricetin significantly reduced the expression of osteoclast-specific markers in mouse bone marrow-derived macrophages, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, the calcitonin receptor, V-ATPase d2, c-fos, and nuclear factor of activated T cells (NFAT) c1. Further investigation revealed that myricetin inhibited osteoclastogenesis through the suppression of the nuclear factor-κB (NF-κB) signaling pathway and mitogen-activated protein kinase (MAPK) pathways involving extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase 1/2 (JNK1/2). While, the inhibition of TNF-α and IL-1β secretion was another reason for the suppressive effect of myricetin on Ti particle-induced osteolysis. Collectively, these findings suggest that myricetin is a potential natural agent for the treatment of periprosthetic osteolysis and other osteoclast-related osteolytic diseases.
钛（Ti）颗粒诱导的假体周围骨溶解和随后的无菌性松动是全髋关节置换失败的主要原因。本研究旨在评估杨梅素对 Ti 颗粒诱导的骨溶解和破骨细胞形成的影响。我们证明，杨梅素作为一种天然植物提取物，在小鼠颅骨模型中对 Ti 颗粒诱导的骨溶解具有强大的抑制作用。进一步的组织学分析表明，抑制破骨细胞的形成和功能以及炎症因子的分泌是治疗磨损颗粒诱导的骨溶解的药物的关键靶点。在体外，我们发现杨梅素以剂量依赖的方式抑制核因子-κB 受体激活剂配体（RANKL）介导的破骨细胞分化、骨吸收和 F-肌动蛋白环形成。此外，杨梅素显著降低了小鼠骨髓来源巨噬细胞中破骨细胞特异性标志物的表达，包括抗酒石酸酸性磷酸酶（TRAP）、组织蛋白酶 K、降钙素受体、V-ATPase d2、c-fos 和激活 T 细胞的核因子（NFAT）c1。进一步的研究表明，杨梅素通过抑制核因子-κB（NF-κB）信号通路和丝裂原激活蛋白激酶（MAPK）通路，包括细胞外信号调节激酶 1/2（ERK1/2）、p38 和 c-Jun N-末端激酶 1/2（JNK1/2），抑制破骨细胞的形成。而抑制 TNF-α和 IL-1β的分泌是杨梅素抑制 Ti 颗粒诱导的骨溶解的另一个原因。总之，这些发现表明杨梅素是治疗假体周围骨溶解和其他与破骨细胞相关的溶骨性疾病的一种有潜力的天然药物。
