School of Stomatology, Dalian Medical University, Dalian, Liaoning, China.
Department of Basic Science of Stomatology, Shanghai Stomatological Hospital, Fudan University, Shanghai, China.
Drug Deliv. 2023 Dec;30(1):2169414. doi: 10.1080/10717544.2023.2169414.
Icariin (ICA) played an important role in the treatment of inflammatory bone defects. However, pharmacokinetic studies have shown that its poor bioavailability limited its application. In this context, we isolated bovine milk-derived sEV and prepared sEV-ICA to improve the osteogenic effect of ICA. In this study, we successfully constructed sEV-ICA. sEV-ICA was found to have significantly higher osteogenic efficiency than ICA in cell culture and cranial bone defect models. Mechanistically, bioinformatics analysis predicted that signal transducers and activators of transcription 5 (STAT5a) may bind to the GJA1 promoter, while luciferase activity assays and chromatin immunoprecipitation (ChIP) experiments confirmed that STAT5a directly binded to the GJA1 promoter to promote osteogenesis. We proved that compared with ICA, sEV-ICA showed a better effect of promoting bone repair in vivo and in vitro. In addition, sEV-ICA could promote osteogenesis by promoting the combination of STAT5a and GJA1 promoter. In summary, as a complex drug delivery system, sEV-ICA constituted a rapid and effective method for the treatment of bone defects and could improve the osteogenic activity of ICA.
淫羊藿苷（ICA）在炎性骨缺损的治疗中发挥着重要作用。然而，药代动力学研究表明，其生物利用度差限制了其应用。在这种情况下，我们分离了牛源乳衍生的外泌体并制备了 sEV-ICA，以提高 ICA 的成骨作用。在本研究中，我们成功构建了 sEV-ICA。细胞培养和颅骨缺损模型研究表明，sEV-ICA 比 ICA 具有更高的成骨效率。从机制上讲，生物信息学分析预测转录激活因子 5（STAT5a）可能与 GJA1 启动子结合，而荧光素酶活性测定和染色质免疫沉淀（ChIP）实验证实 STAT5a 直接与 GJA1 启动子结合，促进成骨。我们证明，与 ICA 相比，sEV-ICA 在体内和体外均表现出更好的促进骨修复的效果。此外，sEV-ICA 可以通过促进 STAT5a 与 GJA1 启动子的结合来促进成骨。总之，作为一种复杂的药物传递系统，sEV-ICA 构成了治疗骨缺损的快速有效方法，并可以提高 ICA 的成骨活性。
