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Bone Marrow Mesenchymal Stem Cells-Derived Exosomal MicroRNA-150-3p Promotes Osteoblast Proliferation and Differentiation in Osteoporosis
Human Gene Therapy ( IF 3.9 ) Pub Date : 2021-07-19 , DOI: 10.1089/hum.2020.005
Min Qiu 1 , Shuheng Zhai 1 , Qin Fu 1 , Da Liu 2
Affiliation  

At present, much more studies have focused on the role of microRNAs in osteoporosis, but the more specific role of microRNA-150-3p (miR-150-3p) in osteoporosis still needs full exploration. We aim at investigating the role of miR-150-3p in osteoporosis and at exploring the related mechanisms. Bone marrow mesenchymal stem cells (BMSCs) were cultured, from which exosomes were isolated. Osteoporosis models were established by ovariectomy and injected with transfected BMSCs exosomes. Bone formation markers in serum, histopathological changes and miR-150-3p, runt-related transcription factor 2 (Runx2) and Osterix expression, and osteoblast apoptosis in femoral tissues were detected. Osteoblasts were isolated and co-cultured with the transfected BMSCs-derived exosomes. Osteoblast proliferation, cell differentiation, and apoptosis, along with miR-150-3p, Runx2, and Osterix expression in osteoblasts were detected. In vivo experiment demonstrated that miR-150-3p, Runx2, and Osterix expression was decreased whereas bone formation markers were decreased in osteoporosis. BMSCs exosomes attenuated osteoporosis, which was further improved by upregulated miR-150-3p in exosomes whereas it was impaired by downregulated miR-150-3p in exosomes. In vitro experiments declared decreased miR-150-3p, Runx2, and Osterix expression; suppressed proliferation; and encouraged apoptosis in osteoblasts in osteoporosis. BMSCs exosomes promoted osteoblast proliferation and differentiation and inhibited apoptosis, which was strengthened by raised exosomal miR-150-3p whereas it was disrupted by inhibited exosomal miR-150-3p. Our study elucidates that exosomal miR-150-3p promotes osteoblast proliferation and differentiation in osteoporosis and provides a new clue for the treatment of patients with osteoporosis.

中文翻译:

骨髓间充质干细胞衍生的外泌体 MicroRNA-150-3p 促进骨质疏松症中成骨细胞的增殖和分化

目前,更多的研究集中在microRNAs在骨质疏松症中的作用,但更具体的microRNA-150-3p(miR-150-3p)在骨质疏松症中的作用仍需充分探索。我们旨在研究 miR-150-3p 在骨质疏松症中的作用并探索相关机制。培养骨髓间充质干细胞 (BMSCs),从中分离外泌体。通过卵巢切除术建立骨质疏松模型并注射转染的BMSCs外泌体。检测血清骨形成标志物、组织病理学变化和 miR-150-3p、runt 相关转录因子 2 (Runx2) 和 Osterix 的表达,以及股骨组织中成骨细胞的凋亡。分离成骨细胞并与转染的骨髓间充质干细胞衍生的外泌体共培养。成骨细胞增殖、细胞分化和凋亡,以及 miR-150-3p,体内实验表明,在骨质疏松症中,miR-150-3p、Runx2 和 Osterix 表达降低,而骨形成标志物降低。BMSCs 外泌体减轻骨质疏松症,外泌体中上调 miR-150-3p 可进一步改善骨质疏松症,而外泌体中 miR-150-3p 下调会损害骨质疏松症。体外实验表明 miR-150-3p、Runx2 和 Osterix 表达降低;抑制增殖;并促进骨质疏松症中成骨细胞的凋亡。骨髓间充质干细胞外泌体促进成骨细胞增殖和分化并抑制细胞凋亡,外泌体 miR-150-3p 升高会增强这种作用,而外泌体 miR-150-3p 会破坏它。我们的研究阐明外泌体miR-150-3p促进骨质疏松症中成骨细胞的增殖和分化,为骨质疏松症患者的治疗提供了新的线索。
更新日期:2021-07-21
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