Department of Orthopedics, the First Affiliated Hospital of Bengbu Medical College, No. 287, Changhuai Road, Bengbu, 233000, Anhui Province, People's Republic of China.
Anhui Province Key Laboratory of Tissue Transplantation (Bengbu Medical College), Bengbu, 233000, Anhui Province, People's Republic of China.
Cell Biol Toxicol. 2023 Aug;39(4):1257-1274. doi: 10.1007/s10565-022-09744-y. Epub 2022 Sep 16.
Extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) are emerged as carriers of therapeutic targets against bone disorders, yet its isolation and purification are limited with recent techniques. Magnetic nanoparticles (MNPs) can load EVs with a unique targeted drug delivery system. We constructed gold-coated magnetic nanoparticles (GMNPs) by decorating the surface of the FeO@SiO core and a silica shell with poly(ethylene glycol) (PEG)-aldehyde (CHO) and examined the role of BMSC-EVs loaded on GMNPs in diabetic osteoporosis (DO). The osteoporosis-related differentially expressed miR-150-5p was singled out by microarray analysis. DO models were then established in Sprague-Dawley rats by streptozotocin injection, where poor expression of miR-150-5p was validated in the bone tissues. Next, GMNP was prepared by combining GMNPs with anti-CD63, after which osteoblasts were co-cultured with the GMNP-BMSC-EVs. The re-expression of miR-150-5p facilitated osteogenesis in osteoblasts. GMNP could promote the enrichment of EVs in the bone tissues of DO rats. BMSC-EVs delivered miR-150-5p to osteoblasts, where miR-150-5p targeted MMP14 and consequently activated Wnt/β-catenin pathway. This effect contributed to the enhancement of osteoblast proliferation and maturation. Furthermore, GMNP enhanced the EV-based delivery of miR-150-5p to regulate the MMP14/Wnt/β-catenin axis, resulting in promotion of osteogenesis. Overall, our findings suggest the potential of GMNP-BMSC-EVs to strengthen osteoblast proliferation and maturation in DO, showing promise as an appealing drug delivery strategy against DO. 1. GMNPs-BMSCs-EVs-miR-150-5p promotes the osteogenesis of DO rats. 2. miR-150-5p induces osteoblast proliferation and maturation by targeting MMP14. 3. Inhibition of MMP14 activates Wnt/β-catenin and increases osteogenesis. 4. miR-150-5p activates the Wnt/β-catenin pathway by downregulating MMP14.
骨髓间充质干细胞来源的细胞外囊泡（BMSC-EVs）作为治疗骨疾病的治疗靶点载体而备受关注，但其分离和纯化受到当前技术的限制。磁性纳米颗粒（MNPs）可以通过在 FeO@SiO 核和硅壳表面修饰聚乙二醇（PEG）-醛（CHO）来负载 EVs，形成独特的靶向药物传递系统。我们通过在 FeO@SiO 核和硅壳表面修饰聚乙二醇（PEG）-醛（CHO），构建了金包裹的磁性纳米颗粒（GMNPs），并用该颗粒负载骨髓间充质干细胞来源的细胞外囊泡（BMSC-EVs），并探讨其在糖尿病性骨质疏松症（DO）中的作用。通过微阵列分析筛选出与骨质疏松症相关的差异表达 miR-150-5p。通过链脲佐菌素注射建立 Sprague-Dawley 大鼠骨质疏松模型，验证 miR-150-5p 在骨组织中的低表达。随后，制备 GMNP 与抗 CD63 结合物，然后与 GMNP-BMSC-EVs 共培养成骨细胞。miR-150-5p 的再表达促进了成骨细胞的成骨作用。GMNP 可以促进 EVs 在 DO 大鼠骨组织中的富集。BMSC-EVs 将 miR-150-5p 递送至成骨细胞，miR-150-5p 靶向 MMP14 并激活 Wnt/β-catenin 通路。该作用有助于促进成骨细胞增殖和成熟。此外，GMNP 增强了基于 EV 的 miR-150-5p 递送，以调节 MMP14/Wnt/β-catenin 轴，从而促进成骨作用。总的来说，我们的研究结果表明，GMNP-BMSC-EVs 有潜力在 DO 中增强成骨细胞的增殖和成熟，为治疗 DO 提供了一种有吸引力的药物递送策略。
