Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), School of Medicine , Shanghai Jiao Tong University , Shanghai 200080 , China.
Graduate Management Unit, Shanghai Changhai Hospital , Second Military Medical University , Shanghai 200433 , China.
Nano Lett. 2019 May 8;19(5):3040-3048. doi: 10.1021/acs.nanolett.9b00287. Epub 2019 Apr 23.
Exosomes, also known as extracellular vesicles, are naturally occurring, biocompatible, and bioacive nanoparticles ranging from 40 to 150 nm in diameter. Bone-secreted exosomes play important roles in bone homeostasis, the interruption of which can lead to diseases such as osteoporosis, rheumatoid arthritis, and osteopetrosis. Though the relationship between vascular and bone homeostasis has been recognized recently, the role of vascular endothelial cell (EC)-secreted exosomes (EC-Exos) in bone homeostasis is not well understood. Herein, we found that EC-Exos show more efficient bone targeting than osteoblast-derived exosomes or bone marrow mesenchymal stem cell-derived exosomes. We also found that EC-Exos can be internalized by bone marrow-derived macrophages (BMMs) to alter their morphology. EC-Exos can inhibit osteoclast activity in vitro and inhibit osteoporosis in an ovariectomized mouse model. Sequencing of exosome miRNA revealed that miR-155 was highly expressed in EC-Exos-treated BMMs. The miR-155 level in EC-Exos was much higher than that in BMMs and ECs, indicating that miR-155 was endogenous cargo of EC-derived vesicles. Blockage of BMMs miR-155 levels reversed the suppression by EC-Exos of osteoclast induction, confirming that exosomal miR-155 may have therapeutic potential against osteoporosis. Taken together, our findings suggest that EC-Exos may be utilized as a bone targeting and nontoxic nanomedicine for the treatment of bone resorption disorders.
外泌体，也称为细胞外囊泡，是直径为 40 至 150nm 的天然存在的、生物相容的和生物活性的纳米颗粒。骨分泌的外泌体在骨稳态中发挥重要作用，其中断可导致骨质疏松症、类风湿性关节炎和骨质增生症等疾病。尽管血管和骨稳态之间的关系最近已被认识到，但血管内皮细胞（EC）分泌的外泌体（EC-Exos）在骨稳态中的作用尚不清楚。在此，我们发现 EC-Exos 比成骨细胞来源的外泌体或骨髓间充质干细胞来源的外泌体具有更高的骨靶向效率。我们还发现 EC-Exos 可被骨髓来源的巨噬细胞（BMMs）内化，从而改变其形态。EC-Exos 可在体外抑制破骨细胞活性，并抑制去卵巢小鼠模型中的骨质疏松症。外泌体 miRNA 测序显示，miR-155 在 EC-Exos 处理的 BMMs 中高表达。EC-Exos 中的 miR-155 水平远高于 BMMs 和 ECs，表明 miR-155 是 EC 来源囊泡的内源性货物。阻断 BMMs 的 miR-155 水平可逆转 EC-Exos 对破骨细胞诱导的抑制作用，证实外泌体 miR-155 可能具有治疗骨质疏松症的潜力。总之，我们的研究结果表明，EC-Exos 可作为一种靶向骨的、无毒的纳米药物，用于治疗骨吸收紊乱。
