Aseptic loosening (AL) is considered a significant cause of prosthesis revision after arthroplasty and a crucial factor in the longevity of an artificial joint prosthesis. The development of AL is primarily attributed to a series of biological reactions, such as peri-prosthetic osteolysis (PPO) induced by wear particles around the prosthesis. Chronic inflammation of the periprosthetic border tissue and hyperactivation of osteoclasts are key factors in this process, which are induced by metallic wear particles like titanium particles (TiPs). In our in vitro study, we observed that TiPs significantly enhanced the expression of inflammation-related genes, including COX-2, IL-1β and IL-6. Through screening a traditional Chinese medicine database, we identified byakangelicol, a traditional Chinese medicine molecule that targets COX-2. Our results demonstrated that byakangelicol effectively inhibited TiPs-stimulated osteoclast activation. Mechanistically, we found that byakangelicol suppressed the expression of COX-2 and related pro-inflammatory factors by modulating macrophage polarization status and NF-κB signaling pathway. The in vivo results also demonstrated that byakangelicol effectively inhibited the expression of inflammation-related factors, thereby significantly alleviating TiPs-induced cranial osteolysis. These findings suggested that byakangelicol could potentially be a promising therapeutic approach for preventing PPO.

中文翻译：

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Byakangelicol 通过 COX-2/NF-κB 信号通路抑制 TiPs 刺激的破骨细胞生成和骨破坏


无菌性松动（AL）被认为是关节置换术后假体翻修的重要原因，也是人工关节假体寿命的关键因素。 AL的发生主要归因于一系列生物反应，例如假体周围磨损颗粒引起的假体周围骨溶解（PPO）。假体周围边缘组织的慢性炎症和破骨细胞的过度激活是这一过程的关键因素，这是由钛颗粒（TiP）等金属磨损颗粒引起的。在我们的体外研究中，我们观察到 TiP 显着增强了炎症相关基因的表达，包括 COX-2、IL-1β 和 IL-6。通过筛选中药数据库，我们鉴定出了一种针对COX-2的中药分子byakangelicol。我们的结果表明，byakangelicol 有效抑制 TiPs 刺激的破骨细胞活化。从机制上讲，我们发现 byakangelicol 通过调节巨噬细胞极化状态和 NF-κB 信号通路来抑制 COX-2 和相关促炎因子的表达。体内结果还表明，byakangelicol可有效抑制炎症相关因子的表达，从而显着减轻TiPs引起的颅骨溶解。这些发现表明，byakangelicol 可能是预防 PPO 的一种有前景的治疗方法。