环状 RNA422 通过 SP7/LRP5 轴增强早期骨整合过程中骨髓间充质干细胞的成骨分化。
circRNA422 enhanced osteogenic differentiation of bone marrow mesenchymal stem cells during early osseointegration through the SP7/LRP5 axis.
机构信息
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310006, China.
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310006, China.
出版信息
Mol Ther. 2022 Oct 5;30(10):3226-3240. doi: 10.1016/j.ymthe.2022.05.020. Epub 2022 May 31.
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（circRNAs）在生物活性中发挥重要作用，特别是在调节干细胞的成骨分化方面。然而，目前尚无研究报道 circRNAs 在早期骨整合中的作用。在这里，我们从在喷砂、大颗粒、酸蚀钛表面培养的大鼠骨髓间充质干细胞（BMSCs）中鉴定到一种新的 circRNA，circRNA422。结果表明，circRNA422 显著增强了 BMSCs 的成骨分化，碱性磷酸酶、SP7 转录因子（SP7/osterix）和脂蛋白受体相关蛋白 5（LRP5）的表达水平增加。circRNA422 的沉默则产生了相反的效果。LRP5 启动子上有两个 SP7 结合位点，表明 SP7 和 LRP5 之间存在直接的调控关系。circRNA422 可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。
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