Department of Orthopedics, Bengbu Medical University Affiliated to First Hospital, Bengbu 233000, Anhui Province, China; Anhui Province Key Laboratory of Tissue Transplantation (Bengbu Medical College), 2600 Donghai Avenue, Bengbu 233030, Anhui Province, China.
Department of Orthopedics, Bengbu Medical University Affiliated to First Hospital, Bengbu 233000, Anhui Province, China; Anhui Province Key Laboratory of Tissue Transplantation (Bengbu Medical College), 2600 Donghai Avenue, Bengbu 233030, Anhui Province, China.
Cell Signal. 2024 Jun;118:111055. doi: 10.1016/j.cellsig.2024.111055. Epub 2024 Jan 20.
Diabetic osteoporosis (DO) is a significant complication of diabetes, characterized by a decrease in bone mineral density and an increase in fracture risk. Magnetic nanoparticles (GMNPs) have emerged as potential drug carriers for various therapeutic applications. This study investigated the molecular mechanism of GMNPs loaded with bone marrow mesenchymal stem cell (BMSC) derived extracellular vesicles (EVs) overexpressing MEG3 target miR-3064-5p to induce NR4A3 for treating DO in rats. Initial analysis was carried out on GEO datasets GSE7158 and GSE62589, revealing a notable downregulation of NR4A3 in osteoporotic samples. Subsequent in vitro studies demonstrated the effective uptake of BMSC-EVs-MEG3 by osteoblasts and its potential to inhibit miR-3064-5p, activating the PINK1/Parkin signaling pathway and thus promoting mitochondrial autophagy, osteoblast proliferation, and differentiation. In vivo, experiments using DO rat models further substantiated the therapeutic efficacy of GMNPE-EVs-MEG3 in alleviating osteoporosis symptoms. In conclusion, GMNPs loaded with BMSC-EVs, through the delivery of MEG3 targeting miR-3064-5p, can effectively promote NR4A3 expression, activate the PINK1/Parkin pathway, and thereby enhance osteoblast proliferation and differentiation, offering a promising treatment for DO.
糖尿病性骨质疏松症（DO）是糖尿病的一种严重并发症，其特征是骨密度降低和骨折风险增加。磁性纳米颗粒（GMNPs）已成为各种治疗应用的潜在药物载体。本研究探讨了负载骨髓间充质干细胞（BMSC）衍生的外泌体（EVs）过表达 MEG3 靶向 miR-3064-5p 的 GMNPs 诱导 NR4A3 治疗大鼠 DO 的分子机制。首先对 GEO 数据集 GSE7158 和 GSE62589 进行了分析，结果表明骨质疏松样本中 NR4A3 明显下调。随后的体外研究表明，BMSC-EVs-MEG3 可被成骨细胞有效摄取，并能抑制 miR-3064-5p，激活 PINK1/Parkin 信号通路，从而促进线粒体自噬、成骨细胞增殖和分化。在体内，用 DO 大鼠模型进行的实验进一步证实了 GMNPE-EVs-MEG3 缓解骨质疏松症状的治疗效果。总之，负载 BMSC-EVs 的 GMNPs 通过递送 MEG3 靶向 miR-3064-5p，可有效促进 NR4A3 的表达，激活 PINK1/Parkin 通路，从而增强成骨细胞的增殖和分化，为 DO 的治疗提供了一种有前景的方法。
