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| 姜黄素预处理BMSC外泌体复合GelMA水凝胶促骨质疏松性骨折愈合及机制 |
| Curcumin pretreatment of BMSC exosomes combined with GelMA hydrogel promotes osteoporotic fracture healing and its mechanism |
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| DOI：10.3969/j.issn.1006-7108.2026.10.003 |
| 中文关键词: 骨质疏松性骨折 姜黄素 Wnt/β-连环蛋白 间充质干细胞 水凝胶 外泌体 |
| 英文关键词:osteoporotic fracture curcumin Wnt/β-catenin mesenchymal stem cells hydrogel exosomes |
| 基金项目:广东省自然科学基金项目（2021A1515010725）；广东省普通高校特色创新类专项（2024KTSCX115）；广东省中医药局科研项目-面上项目（20261180）；广州市科学技术计划项目（2023B03J0056） |
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| 中文摘要: |
| 目的 探究姜黄素（curcumin，CUR）预处理的骨髓间充质干细胞外泌体（bone mesenchymal stem cells exosomes，BMSC-Exos）经GelMA水凝胶负载后，能否促进骨质疏松性骨折（osteoporotic fracture，OPF）愈合及其作用机制。方法 收集经CUR预处理（CURMSC-Exos）与未预处理（NCMSC-Exos）的BMSC-Exos，体外通过碱性磷酸酶染色（ALP）、茜素红染色（ARS）检测其对细胞骨矿化能力的影响；划痕实验检测细胞迁移率；免疫印迹法（Western Blot）检测Col1a1、Runx2、p-Stat3、Wnt1、β-catenin表达水平。检测GelMA水凝胶的载药性能，将收集的BMSC-Exos于GelMA水凝胶上负载，形成负载体系（CURMSC-Exo-GelMA、NCMSC-Exo-GelMA）。体内构建OPF模型，分别使用CURMSC-Exo-GelMA、NCMSC-Exo-GelMA及GelMA干预，通过Micro-CT验证OP模型构建成功并利用X线观察骨折愈合情况；HE/Masson染色法检测骨组织病理形态。结果 体外实验显示，与NCMSC-Exos相比，CURMSC-Exos组ALP与ARS染色更深且划痕愈合更快；成骨相关蛋白Col1a1、Runx2在CURMSC-Exos组中表达更高（P＜0.05）。体内实验显示，与NCMSC-Exo-GelMA组相比，CURMSC-Exo-GelMA组骨折断端更快实现骨性连接，断端间隙被成熟骨性骨痂紧密填充。Western Blot结果显示CURMSC-Exos显著上调p-Stat3及Wnt/β-catenin的表达（P＜0.05）。结论 GelMA水凝胶负载CURMSC-Exos能够促进OPF的骨愈合，这可能与STAT3/Wnt/β-catenin信号的激活有关。 |
| 英文摘要: |
| Objective To investigate whether exosomes derived from bone mesenchymal stem cells (BMSC-Exos) pretreated with curcumin (CUR) can promote the healing of osteoporotic fractures (OPF) when loaded onto GelMA hydrogel, as well as to explore the underlying mechanism. Methods BMSC-Exos were collected from BMSCs with CUR pretreatment (CURMSC-Exos) and without pretreatment (NCMSC-Exos). In vitro experiments were carried out as follows: Alkaline Phosphatase (ALP) staining and Alizarin Red S (ARS) staining were used to detect the effect of these exosomes on the osteogenic mineralization capacity of cells; scratch assay was employed to measure cell migration rate; Western blot was used to detect the expression levels of Col1a1, Runx2, p-Stat3, Wnt1, and β-catenin. While detecting the drug-loading performance of GelMA hydrogel, the collected BMSC-Exos were loaded onto GelMA hydrogel to form exosome-loaded systems, namely CURMSC-Exo-GelMA and NCMSC-Exo-GelMA. An in vivo OPF model was established, and the model was treated with CURMSC-Exo-GelMA, NCMSC-Exo-GelMA, and GelMA respectively. Micro-CT was used to verify the successful establishment of the OP model, while X-ray was applied to observe the fracture healing process; Hematoxylin-Eosin staining and Masson staining were performed to examine the pathological morphology of bone tissue. Results In vitro experiments showed that compared with the NCMSC-Exos group, the CURMSC-Exos group exhibited deeper ALP and ARS staining, and faster scratch wound healing. Additionally, the expression levels of osteogenesis-related proteins Col1a1 and Runx2 were significantly higher in the CURMSC-Exos group (P<0.05). In vivo experiments revealed that compared with the NCMSC-Exo-GelMA group, the CURMSC-Exo-GelMA group achieved faster bony union at the fracture site, with the fracture gap tightly filled by mature bony callus. Western blot results indicated that CURMSC-Exos significantly upregulated the expression of p-Stat3 and proteins in the Wnt/β-catenin pathway (P<0.05). Conclusion GelMA hydrogel loaded with CURMSC-Exos can promote bone healing of OPF, which may be associated with the activation of the STAT3/Wnt/β-catenin signaling pathway. |
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