Chen Ping, Wu Long, Zhang Shuai, Jin Qunhua, Sun Kening
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.
Front Cell Dev Biol. 2025 Mar 6;13:1511577. doi: 10.3389/fcell.2025.1511577. eCollection 2025.
Wear particle-induced periprosthetic osteolysis is a prevalent issue that frequently leads to the failure of joint replacements, necessitating the development of effective therapeutic strategies. In this study, we established a mouse model of prosthetic loosening and evaluated the therapeutic effects of targeting tumor necrosis factor-alpha () and wingless-type MMTV integration site family, member 3A () on osteolysis. knockdown reduced inflammation and osteoclast-related gene expression, while overexpression increased osteoblast-related gene expression. Notably, the combination of these interventions showed superior efficacy in inhibiting osteolysis compared to monotherapy. Biomechanical imaging and histological staining revealed that combined therapy enhanced bone density and minimized the gaps between the peri-prosthetic bone and the prosthesis, reducing fibrous connective tissue proliferation. Adeno-associated virus-mediated gene therapy was found to be safe, with no adverse effects observed in liver, brain, spleen, and kidney tissues. Our findings suggest that combining silencing with overexpression may be a promising approach for treating particle-induced peri-implant osteolysis and warrants further clinical investigation.
磨损颗粒诱导的假体周围骨溶解是一个普遍存在的问题，常常导致关节置换失败，因此需要开发有效的治疗策略。在本研究中，我们建立了假体松动的小鼠模型，并评估了靶向肿瘤坏死因子-α（TNF-α）和无翅型MMTV整合位点家族成员3A（Wnt3a）对骨溶解的治疗效果。TNF-α基因敲低减少了炎症和破骨细胞相关基因的表达，而Wnt3a过表达增加了成骨细胞相关基因的表达。值得注意的是，与单一疗法相比，这些干预措施的联合应用在抑制骨溶解方面显示出更好的疗效。生物力学成像和组织学染色显示，联合治疗提高了骨密度，并使假体周围骨与假体之间的间隙最小化，减少了纤维结缔组织增生。发现腺相关病毒介导的基因治疗是安全的，在肝、脑、脾和肾组织中未观察到不良反应。我们的研究结果表明，将TNF-α沉默与Wnt3a过表达相结合可能是治疗颗粒诱导的种植体周围骨溶解的一种有前景的方法，值得进一步的临床研究。
