Circular RNAs (circRNAs) play an important role in biological activities, especially in regulating osteogenic differentiation of stem cells. However, no studies have reported the role of circRNAs in early osseointegration. Here we identified a new circRNA, circRNA422, from rat bone marrow mesenchymal stem cells (BMSCs) cultured on sandblasted, large-grit, acid-etched titanium surfaces. The results showed that circRNA422 significantly enhanced osteogenic differentiation of BMSCs with increased expression levels of alkaline phosphatase, the SP7 transcription factor (SP7/osterix), and lipoprotein receptor-related protein 5 (LRP5). Silencing of circRNA422 had opposite effects. There were two SP7 binding sites on the LRP5 promoter, indicating a direct regulatory relationship between SP7 and LRP5. circRNA422 could regulate early osseointegration in in vivo experiments. These findings revealed an important function of circRNA422 during early osseointegration. Therefore, circRNA422 may be a potential therapeutic target for enhancing implant osseointegration.

环状RNA（circRNA）在生物活性中发挥着重要作用，特别是在调节干细胞的成骨分化方面。然而，尚无研究报道 circRNA 在早期骨整合中的作用。在这里，我们从在喷砂、大砂粒、酸蚀钛表面上培养的大鼠骨髓间充质干细胞 (BMSC) 中鉴定出一种新的 circRNA，circRNA422。结果显示，circRNA422显着增强BMSCs的成骨分化，同时增加碱性磷酸酶、SP7转录因子（SP7/osterix）和脂蛋白受体相关蛋白5（LRP5）的表达水平。 circRNA422 的沉默产生相反的效果。 LRP5启动子上有两个SP7结合位点，表明SP7和LRP5之间存在直接调控关系。 circRNA422可以在体内实验中调节早期骨整合。这些发现揭示了 circRNA422 在早期骨整合过程中的重要功能。因此，circRNA422可能是增强种植体骨整合的潜在治疗靶点。