Qiu Min, Zhai Shuheng, Fu Qin, Liu Da
Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Hum Gene Ther. 2021 Jul;32(13-14):717-729. doi: 10.1089/hum.2020.005. Epub 2021 Jan 22.
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. 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. 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.
目前,已有更多研究聚焦于微小RNA在骨质疏松症中的作用,但微小RNA-150-3p(miR-150-3p)在骨质疏松症中更具体的作用仍有待充分探索。我们旨在研究miR-150-3p在骨质疏松症中的作用,并探索其相关机制。培养骨髓间充质干细胞(BMSCs),从中分离出外泌体。通过卵巢切除建立骨质疏松症模型,并注射转染的BMSCs外泌体。检测血清中的骨形成标志物、组织病理学变化以及股骨组织中miR-150-3p、 runt相关转录因子2(Runx2)和Osterix的表达,以及成骨细胞凋亡情况。分离成骨细胞并与转染的BMSCs来源的外泌体共培养。检测成骨细胞增殖、细胞分化和凋亡情况,以及成骨细胞中miR-150-3p、Runx2和Osterix的表达。实验表明,骨质疏松症中miR-150-3p、Runx2和Osterix表达降低,同时骨形成标志物减少。BMSCs外泌体减轻了骨质疏松症,外泌体中上调miR-150-3p可进一步改善骨质疏松症,而外泌体中下调miR-150-3p则会损害骨质疏松症。实验表明,骨质疏松症中成骨细胞中miR-150-3p、Runx2和Osterix表达降低,增殖受到抑制,凋亡增加。BMSCs外泌体促进成骨细胞增殖和分化并抑制凋亡,外泌体中miR-150-3p升高可增强此作用,而外泌体中miR-150-3p受到抑制则会破坏此作用。我们的研究表明,外泌体miR-150-3p在骨质疏松症中促进成骨细胞增殖和分化,为骨质疏松症患者的治疗提供了新线索。