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血管内皮细胞来源的外泌体 miR-5p-72106_14 调控骨髓间充质干细胞的命运决定。

Exosome-derived miR-5p-72106_14 in vascular endothelial cells regulates fate determination of BMSCs.

机构信息

Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China; Institute of Clinical Pharmacy, Central South University, Changsha, China.

Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, China.

出版信息

Toxicol Appl Pharmacol. 2024 Jan;482:116793. doi: 10.1016/j.taap.2023.116793. Epub 2023 Dec 18.

Abstract

Vascular endothelial cells have recently been shown to be associated with osteogenic activity. However, the mechanism of vascular endothelial cells promoting osteogenesis is unclear. Here, we found that exosomes secreted from human microvascular endothelial cells (HMEC-1) promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and inhibited adipogenic differentiation. Aged and ovariectomy mice treated with exosomes showed increased bone formation and decreased lipid accumulation in the bone marrow cavity. Additionally, we screened out novel exosomal miR-5p-72106_14 by miRNA-seq and confirmed that miR-5p-72106_14 promoted osteogenic differentiation and inhibited adipogenic differentiation of BMSCs by inhibiting STAT1. Our results suggest that vascular endothelial cell-derived exosomes are involved in BMSC differentiation and exosomal miR-5p-72106_14 is a major factor in regulating fate determination of BMSCs.

摘要

血管内皮细胞最近被证明与成骨活性有关。然而,血管内皮细胞促进成骨的机制尚不清楚。在这里,我们发现人微血管内皮细胞(HMEC-1)分泌的外泌体促进骨髓间充质干细胞(BMSCs)的成骨分化,并抑制脂肪生成分化。用外泌体处理的老年和去卵巢小鼠表现出增加的骨形成和减少的骨髓腔中脂质积累。此外,我们通过 miRNA-seq 筛选出新型外泌体 miR-5p-72106_14,并证实 miR-5p-72106_14 通过抑制 STAT1 促进 BMSCs 的成骨分化和抑制脂肪生成分化。我们的结果表明,血管内皮细胞衍生的外泌体参与 BMSC 分化,外泌体 miR-5p-72106_14 是调节 BMSCs 命运决定的主要因素。

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