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骨髓间充质干细胞分泌的外泌体携带的LncRNA SNHG14通过介导miR-27a-3p/LMNB1轴调节骨质疏松症中的成骨作用和脂肪生成。

LncRNA SNHG14 Delivered by Bone Marrow Mesenchymal Stem Cells-Secreted Exosomes Regulates Osteogenesis and Adipogenesis in Osteoporosis by Mediating the miR-27a-3p/LMNB1 Axis.

作者信息

Tang Jin-Shan, Yu Huai-Xi, Ruan Ru-Xin, Chen Rui, Zhu Zi-Qiang

机构信息

Department of Joint Surgery, Huai'an Second People's Hospital (The Affiliated Huaian Hospital of Xuzhou Medical University), Huai'an City, Jiangsu Province, China.

Department of Orthopaedics, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou City, Jiangsu Province, China.

出版信息

Kaohsiung J Med Sci. 2025 May;41(5):e70004. doi: 10.1002/kjm2.70004. Epub 2025 Mar 7.

Abstract

The purpose of this study was to investigate the role of LncRNA SNHG14 delivered by bone marrow mesenchymal stem cells-secreted exosomes (BMSC-Exos) in osteoporosis (OP). BMSCs and BMSCs-Exos were isolated and identified. BMSCs were transfected, from which BMSCs-Exos were collected. The treated BMSCs-Exos were co-cultured with BMSCs. After osteogenic induction of BMSCs, the calcification was analyzed by alizarin red S staining. After adipogenic induction of BMSCs, lipid droplets were detected by oil red O staining. Glycerol-3-phosphate dehydrogenase activity was measured in BMSCs. OVX mouse models were established and treated with BMSC-EXOs. HE staining and IHC staining were performed on the femurs of mice. The interaction between SNHG14, miR-27a-3p, and LMNB1 was evaluated by luciferase reporter gene assay and RIP assay. Gene levels were assessed using RT-qPCR and Western blot, respectively. BMSC-Exos promoted osteogenic-adipogenic balance of BMSCs. SNHG14 enhanced the promoting effect of BMSCs-Exos on the balance of osteogenesis and adipogenesis of BMSCs. SNHG14 directly bound miR-27a-3p. SNHG1 mediated osteogenic-adipogenic balance in BMSCs via miR-27a-3p. LMNB1 was a target gene of miR-27a-3p. LMNB1 was involved in the process of SNHG14 regulating osteogenic-adipogenic balance in BMSCs. SNHG14 overexpression promoted bone formation and alleviated OP in vivo. SNHG14 delivered by BMSCs-Exos regulates osteogenesis and adipogenesis in OP by mediating the miR-27a-3p/LMNB1 axis.

摘要

本研究旨在探讨骨髓间充质干细胞分泌的外泌体(BMSC-Exos)携带的长链非编码RNA SNHG14在骨质疏松症(OP)中的作用。分离并鉴定了BMSC和BMSC-Exos。对BMSC进行转染,从中收集BMSC-Exos。将处理后的BMSC-Exos与BMSC共培养。对BMSC进行成骨诱导后,通过茜素红S染色分析钙化情况。对BMSC进行成脂诱导后,通过油红O染色检测脂滴。测定BMSC中的甘油-3-磷酸脱氢酶活性。建立去卵巢(OVX)小鼠模型并用BMSC-EXOs进行治疗。对小鼠股骨进行苏木精-伊红(HE)染色和免疫组化(IHC)染色。通过荧光素酶报告基因检测和RNA免疫沉淀(RIP)检测评估SNHG l4、miR-27a-3p和核纤层蛋白B1(LMNB1)之间的相互作用。分别使用逆转录-定量聚合酶链反应(RT-qPCR)和蛋白质免疫印迹法评估基因水平。BMSC-Exos促进了BMSC的成骨-成脂平衡。SNHG14增强了BMSC-Exos对BMSC成骨与成脂平衡的促进作用。SNHG14直接与miR-27a-3p结合。SNHG1通过miR-27a-3p介导BMSC中的成骨-成脂平衡。LMNB1是miR-27a-3p的靶基因。LMNB1参与了SNHG14调节BMSC中成骨-成脂平衡的过程。SNHG14过表达促进体内骨形成并减轻OP。BMSC-Exos携带的SNHG14通过介导miR-27a-3p/LMNB1轴调节OP中的成骨和成脂过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba42/12087430/41a79c920e3f/KJM2-41-e70004-g001.jpg

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