Department of Orthopedic Surgery, Ningxia Medical University, 1160 Shengli Street, Xingqing Area, Yinchuan, Ningxia, P.R. China 750004.
Department of Orthopedics, General Hospital of Ningxia Medical University, 804 Shengli Street, Xingqing Area, Yinchuan, Ningxia, P.R. China 750004.
Biosci Rep. 2021 Jan 29;41(1). doi: 10.1042/BSR20203003.
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. The present study aimed to investigate the possible effect and mechanism of strontium ranelate (SR), 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 its 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.
假体周围骨溶解导致的无菌性松动是限制全关节置换术 (TJA) 使用寿命的主要并发症。磨损颗粒会在假体周围组织中引发慢性炎症反应，并使骨平衡转向骨吸收。本研究旨在探讨临床安全的骨质疏松药物雷奈酸锶（SR）对颗粒诱导的假体周围骨溶解的可能作用和机制。36 只雌性 C57BL/6j 小鼠接受胫骨 Ti 钉植入术，建立无菌性松动动物模型。12 周后，微 CT 结果表明雷奈酸锶可抑制假体周围骨吸收。在体外，使用 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，建立无菌性松动细胞模型。碱性磷酸酶（ALP）检测、免疫荧光和流式细胞术的结果表明，雷奈酸锶可以调节 OPG/RANKL 的表达，促进成骨细胞的分化和矿化，并抑制其凋亡。此外，我们还揭示了 SR 通过下调骨硬化蛋白来发挥其治疗作用，从而激活 Wnt/β-catenin 信号通路。因此，这项研究表明，雷奈酸锶可能是预防和治疗 TJA 后颗粒诱导的无菌性松动的潜在药物。
