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| LncRNA HOTTIP及IGF-2作为骨质疏松症潜在标志物的作用与意义 |
| The role and significance of LncRNA HOTTIP and IGF-2 as potential biomarkers for osteoporosis |
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| DOI：10.3969/j.issn.1006-7108.2026.09.001 |
| 中文关键词: 骨质疏松症 lncRNA HOTTIP IGF-2 生物标志物 差异表达 |
| 英文关键词:osteoporosis LncRNA HOTTIP IGF-2 biomarker differential expression |
| 基金项目:国家自然科学基金（82260442）；广西自然科学基金（2022JJA140036） |
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| 中文摘要: |
| 目的 探讨长链非编码RNA HOTTIP（lncRNA HOTTIP）及胰岛素样生长因子2（insulin-like groth factor 2，IGF-2）在骨质疏松症（osteoporosis，OP）中的表达特征及其临床意义。方法 （1）体外诱导小鼠骨髓间充质干细胞（bone marrow mesenchymal stem cells，BMSCs）成骨分化，于第0、1、2周茜素红染色评估分化程度，采用实时逆转录定量聚合酶链反应（real-time quantitative reverse transcription polymerase chain reaction，RT-qPCR）检测HOTTIP、IGF-2及成骨相关基因表达。（2）建立双侧卵巢切除（bilateral ovariectomy，OVX）诱导的绝经后OP小鼠模型（n=6） 和假手术对照组（n=6），术后8周取股骨行苏木精-伊红染色（hematoxylin and eosin staining, HE染色）观察骨微结构，RT-qPCR检测骨组织HOTTIP及IGF-2表达。（3）收集21例女性OP患者（BMD T≤-2.5）和20例非OP对照者（T＞-2.5）的外周血标本，RT-qPCR检测HOTTIP及IGF-2表达，分析其相关性及与临床指标关系。结果 （1）BMSCs成骨分化过程中，HOTTIP、IGF-2mRNA表达随分化时间延长显著上调（P＜0.05），与矿化结节形成及成骨基因表达趋势一致；（2）OVX组小鼠骨小梁稀疏，骨髓腔增大，骨组织中HOTTIP、IGF-2表达低于假手术组（P＜0.05）；（3）OP组患者外周血HOTTIP、IGF-2表达低于非OP组 （P＜0.05），且二者表达呈显著正相关 （R2=0.6813，P＜0.0001）；ROC曲线分析结果显示二者在疾病诊断方面具有显著的诊断效能（P＜0.05），二者的ROC曲线下面积（AUC）＞0.5。结论 LncRNA HOTTIP与IGF-2在OP中表达下调且密切相关，可能作为OP的潜在保护因子及循环生物标志物，为早期诊断和靶向干预提供新思路。 |
| 英文摘要: |
| Objective To explore the expression characteristics and clinical significance of long non-coding RNA HOTTIP and insulin-like growth factor 2 in osteoporosis. Methods (1) Mouse bone marrow mesenchymal stem cells were induced to osteogenic differentiation in vitro. Alizarin red staining was evaluated at week 0, 1, and 2 to assess the degree of differentiation. RT-qPCR was used to detect the expressions of HOTTIP, IGF-2, and osteogenic-related genes. (2) A postmenopausal osteoporosis mouse model was established by bilateral ovariectomy (n = 6), and a sham operation control group was set up (n = 6). After 8 weeks, the femurs were collected for H&E staining to observe bone microstructure. RT-qPCR was used to detect the expressions of HOTTIP and IGF-2 in bone tissue. (3) Peripheral blood samples were collected from 21 female OP patients (BMD T ≤ -2.5) and 20 non-OP controls (T > -2.5). RT-qPCR was used to detect the expressions of HOTTIP and IGF-2, and their correlation and relationship with clinical indicators were analyzed. Results (1) During the osteogenic differentiation of BMSCs, the mRNA expressions of HOTTIP and IGF-2 significantly increased with the prolongation of differentiation time (P<0.05), which was consistent with the formation of mineralized nodules and the expression trend of osteogenic genes. (2) In the OVX group, the bone trabeculae were sparse, the bone marrow cavity was enlarged, and the expressions of HOTTIP and IGF-2 in the bone tissue were lower than those in the sham operation group (P<0.05). (3) The expressions of HOTTIP and IGF-2 in the peripheral blood of OP patients were lower than those in the non-OP group (P <0.05), and the expressions of the two were significantly positively correlated (R2=0.6813, P <0.0001). The ROC curve analysis results indicated that both of them had significant diagnostic efficacy in disease diagnosis (P < 0.05), and the area under the ROC curve (AUC) of both was greater than 0.5. Conclusion LncRNA HOTTIP and IGF-2 are both down-regulated in osteoporosis and are closely related. They may serve as potential protective factors and circulating biomarkers for osteoporosis, providing new ideas for early diagnosis and targeted intervention. |
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