Aseptic loosening following periprosthetic osteolysis is the primary complication that limits the lifetime of total joint arthroplasty (TJA). The wear particles trigger a chronic inflammation response in the periprosthetic tissue and turn over the bone balance to bone resorption. This study aimed to investigate the possible effect and mechanism of strontium ranelate, a clinically safe drug for osteoporosis, on particle-induced periprosthetic osteolysis. Thirty-six female C57BL/6j mice underwent tibial Ti-nail implantation to establish an animal model of aseptic loosening. After 12 weeks, micro-CT results showed that strontium ranelate could inhibit periprosthetic bone resorption. In vitro, Ti particles were used to stimulate RAW264.7 cell line to collect conditioned medium, and co-culture MC3T3-E1 cell line with conditioned medium to establish a cell model of aseptic loosening. The results of alkaline phosphatase (ALP) detection, immunofluorescence, and flow cytometry demonstrated that strontium ranelate could regulate the expression of OPG/RANKL, promote differentiation and mineralization, and inhibit apoptosis in osteoblasts. Moreover, we revealed that SR's exerted their therapeutic effect by down-regulating sclerostin, thereby activating the Wnt/β-catenin signal pathway. Therefore, this research suggests that strontium ranelate could be a potential drug for the prevention and treatment of particle-induced aseptic loosening post-TJA.

中文翻译：

---

体内和体外雷奈酸锶对 Wnt/β-连环蛋白信号调节钛颗粒诱导的假体周围骨溶解的影响。


假体周围骨溶解后的无菌性松动是限制全关节置换术（TJA）寿命的主要并发症。磨损颗粒会引发假体周围组织的慢性炎症反应，并将骨平衡转变为骨吸收。本研究旨在探讨临床安全的骨质疏松药物雷奈酸锶对颗粒引起的假体周围骨溶解的可能作用和机制。 36只雌性C57BL/6j小鼠进行胫骨Ti-钉植入，建立无菌松动动物模型。 12周后，显微CT结果显示雷奈酸锶可以抑制假体周围骨吸收。在体外，用Ti颗粒刺激RAW264.7细胞系收集条件培养基，并与条件培养基共培养MC3T3-E1细胞系，建立无菌松动细胞模型。碱性磷酸酶（ALP）检测、免疫荧光和流式细胞术结果表明，雷奈酸锶可以调节OPG/RANKL的表达，促进成骨细胞分化和矿化，抑制细胞凋亡。此外，我们发现SR通过下调硬化素发挥治疗作用，从而激活Wnt/β-连环蛋白信号通路。因此，本研究表明雷奈酸锶可能成为预防和治疗 TJA 后颗粒引起的无菌性松动的潜在药物。