Chen Ping, Guo Hao-Hui, Wu Long, Zhang Shuai, Jin Qun-Hua, Sun Ke-Ning
Medical Experiment Center, General Hospital of Ningxia Medical University, Yinchuan, China.
Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, China.
Eur J Med Res. 2025 Mar 29;30(1):216. doi: 10.1186/s40001-025-02452-3.
Aseptic prosthesis loosening caused by wear particles is a major complication in patients with osteoarthritis following total joint replacement. Despite advancements in treatment, the underlying mechanisms remain poorly understood, and effective therapies are still lacking.
In this study, we investigated the effects of titanium particles on osteoclast and osteoblast differentiation through both in vitro and in vivo experiments.
Our findings revealed that titanium particles not only promote the differentiation of RAW264.7 cells into osteoclasts and enhance the secretion of inflammatory factors but also inhibit the differentiation of BMSCs into osteoblasts and reduce the expression of Wnt signaling pathway-related factors. Furthermore, using a mouse model of knee prosthesis loosening and AAV-mediated gene therapy, we demonstrated that the combination of TNF-α interference and Wnt3a overexpression was more effective than single-gene therapy in reducing inflammatory cell infiltration, promoting bone formation, and mitigating bone destruction.
These results highlight the dual role of titanium particles in periprosthetic osteolysis and underscore the potential of a gene therapy strategy targeting both inflammatory factors and the Wnt signaling pathway to improve knee prosthesis loosening. This study provides a scientific foundation for developing novel therapeutic approaches.
磨损颗粒导致的无菌性假体松动是全关节置换术后骨关节炎患者的主要并发症。尽管治疗取得了进展，但其潜在机制仍知之甚少，且仍缺乏有效的治疗方法。
在本研究中，我们通过体外和体内实验研究了钛颗粒对破骨细胞和成骨细胞分化的影响。
我们的研究结果表明，钛颗粒不仅促进RAW264.7细胞向破骨细胞分化并增强炎症因子的分泌，还抑制骨髓间充质干细胞向成骨细胞分化并降低Wnt信号通路相关因子的表达。此外，使用膝关节假体松动小鼠模型和腺相关病毒介导的基因治疗，我们证明肿瘤坏死因子-α干扰和Wnt3a过表达联合治疗在减少炎症细胞浸润、促进骨形成和减轻骨破坏方面比单基因治疗更有效。
这些结果突出了钛颗粒在假体周围骨溶解中的双重作用，并强调了针对炎症因子和Wnt信号通路的基因治疗策略在改善膝关节假体松动方面的潜力。本研究为开发新的治疗方法提供了科学依据。
