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.
The effect of strontium ranelate on titanium particle-induced peri-prosthetic osteolysis regulated by Wnt/β-catenin signaling in vivo and in vitro
- Views Icon Views
- PDF LinkPDF
- Share Icon Share
Bolun Wang, Haohui Guo, Tianxiang Geng, Kening Sun, Liang Zhang, Zhidong Lu, Qunhua Jin; The effect of strontium ranelate on titanium particle-induced peri-prosthetic osteolysis regulated by Wnt/β-catenin signaling in vivo and in vitro. Biosci Rep 2021; BSR20203003. doi: https://doi.org/10.1042/BSR20203003
Download citation file: