LncRNA SNHG1/miR-101-3p/HMGA2轴对骨质疏松大鼠成骨分化影响
The effect of LncRNA SNHG1/miR-101-3p/HMGA2 axis on osteogenic differentiation in osteoporosis rats
  
DOI:10.3969/j.issn.1006-7108.2026.02.001
中文关键词:  长链非编码小核仁RNA宿主基因1  微小RNA-101-3p  高迁移率族蛋白A2  骨质疏松大鼠  成骨细胞  分化
英文关键词:long non-coding small nucleolar RNA host gene 1  microRNA-101-3p  high mobility group protein A2  osteoporosis rats  osteoblasts  differentiation
基金项目:武汉市中医药科研项目(WZ24B06)
作者单位
唐勇1 贾玉俊1* 戴维涛1 罗锟2 1.武汉同济航天城医院骨科, 湖北 武汉 430416 2.武汉市中医医院骨科, 湖北 武汉 430010 
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中文摘要:
      目的 探讨长链非编码RNA(LncRNA)核仁小分子RNA宿主基因1(SNHG1)/微小RNA-101-3p(miR-101-3p)/高迁移率族蛋白A2(HMGA2)对骨质疏松(osteoporosis, OP)大鼠成骨分化的影响。方法 构建OP大鼠模型,提取成骨细胞,通过qRT-PCR法检测LncRNA SNHG1和miR-101-3p的相对表达水平。将细胞分为Control组、Model组、sh-NC组、sh-SNHG1组、sh-SNHG1+inhibitor NC组、sh-SNHG1+miR-101-3p inhibitor组。检测各组成骨细胞LncRNA SNHG1、miR-101-3p和HMGA2 mRNA表达水平(qRT-PCR法)、细胞增殖能力(CCK-8试剂盒法)、细胞凋亡情况(流式细胞术法)、成骨细胞ALP相对活性(ALP试剂盒)、成骨细胞矿化能力(茜红素染色)、成骨细胞中HMGA2、Bax和Bcl 2蛋白表达量,验证miR-101-3p与LncRNA SNHG1、HMGA2之间的靶向关系。结果 Model组相较于Control组成骨细胞中LncRNA SNHG1和HMGA2 mRNA表达水平以及HMGA2、Bax蛋白表达水平、细胞凋亡率显著升高,miR-101-3p相对表达水平以及Bcl 2蛋白表达水平、细胞活力、ALP相对活性、矿化能力显著下降(P<0.05);sh-SNHG1组相较于sh-NC组成骨细胞HMGA2、Bax蛋白表达水平、LncRNA SNHG1和HMGA2 mRNA表达水平、细胞凋亡率明显降低,miR-101-3p相对表达水平以及Bcl 2蛋白表达水平、细胞活力、ALP相对活性、矿化能力显著升高(P<0.05);sh-SNHG1+miR-101-3p inhibitor组相较于sh-SNHG1+inhibitor NC组成骨细胞中HMGA2、Bax蛋白表达水平、LncRNA SNHG1和HMGA2 mRNA表达水平、细胞凋亡率显著升高,miR-101-3p表达水平以及Bcl 2蛋白表达水平、细胞活力、ALP相对活性、矿化能力显著下降(P<0.05)。结论 在OP大鼠成骨细胞中LncRNA SNHG1表达水平显著上调,沉默LncRNA SNHG1的表达可通过靶向上调miR-101-3p的表达、抑制HMGA2的表达,进而减少成骨细胞凋亡、增强成骨细胞矿化能力和ALP活性、促进其增殖分化。
英文摘要:
      Objective To investigate the effects of long non coding RNA (LncRNA) small nucleolar RNA host gene 1 (SNHG1)/microRNA-101-3p (miR-101-3p) /high mobility group protein A2 (HMGA2) on osteogenic differentiation in osteoporosis (OP) rats. Methods An OP rat model was constructed and the osteoblasts were extracted, and the relative expression levels of LncRNA SNHG1 and miR-101-3p were detected using qRT-PCR. The cells were grouped into Control group, Model group, sh-NC group, sh-SNHG1 group, sh-SNHG1+inhibitor NC group, and sh-SNHG1+miR-101-3p inhibitor group. The relative expression levels of LncRNA SNHG1, miR-101-3p, and HMGA2 mRNA in osteoblasts (qRT-PCR method), cell proliferation ability (CCK-8 kit method), apoptosis status (flow cytometry method), relative activity of ALP in osteoblasts (ALP kit), mineralization ability of osteoblasts (eosin staining), and protein expression levels of HMGA2, Bax, and Bcl-2 in osteoblasts were measured. Relevant experiments verified the targeting relationship between miR-101-3p and LncRNA SNHG1 and HMGA2. Results Compared with the Control group, the relative expression levels of LncRNA SNHG1 and HMGA2 mRNA, the expression levels of HMGA2 and Bax proteins, and the apoptosis rate in osteoblasts were greatly higher in the Model group, the relative expression level of miR-101-3p, the expression level of Bcl-2 protein, cell viability, ALP relative activity, and mineralization ability were greatly lower (P<0.05). Compared with the sh-NC group, the relative expression levels of LncRNA SNHG1 and HMGA2 mRNA, the expression levels of HMGA2 and Bax proteins, and the apoptosis rate in osteoblasts were greatly lower in the sh-SNHG1 group, the relative expression level of miR-101-3p, the expression level of Bcl-2 protein, cell viability, ALP relative activity, and mineralization ability were greatly higher (P<0.05). Compared with the sh-SNHG1+inhibitor NC group, the relative expression levels of LncRNA SNHG1 and HMGA2 mRNA, the expression levels of HMGA2 and Bax proteins, and the apoptosis rate in osteoblasts were greatly higher in the sh-SNHG1+miR-101-3p inhibitor group, the relative expression level of miR-101-3p, the expression level of Bcl-2 protein, cell viability, ALP relative activity, and mineralization ability were greatly lower (P<0.05). Conclusion The expression level of LncRNA SNHG1 is greatly upregulated in OP rat osteoblasts. Silencing the expression of LncRNA SNHG1 can upregulate the expression of miR-101-3p and inhibit the expression of HMGA2, thereby reducing osteoblast apoptosis, enhancing osteoblast mineralization ability and ALP activity, and promoting their proliferation and differentiation.
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