| 王 璟,何学智,王 晶,王 婵,刘星辰,刘博阳,苗登顺.长非编码RNA GMDS-DT在骨质疏松发生中的作用和机制探索[J].现代生物医学进展英文版,2024,(18):3407-3414. |
| 长非编码RNA GMDS-DT在骨质疏松发生中的作用和机制探索 |
| Effect and Mechanism of Long Non-coding RNA GMDS-DT in Osteoporosis |
| Received:February 18, 2024 Revised:March 10, 2024 |
| DOI：10.13241/j.cnki.pmb.2024.18.002 |
| 中文关键词: 骨质疏松 长非编码RNA GMDS-DT HNRNPA1 |
| 英文关键词: OP Long non-coding RNA GMDS-DT HNRNPA1 |
| 基金项目:国家自然科学基金面上项目（82172504） |
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| 中文摘要: |
| 摘要 目的：探究长非编码RNA（LncRNA）GMDS-DT在骨质疏松发生发展中的作用及其潜在分子机制。方法：利用测序筛选并通过qRT-PCR验证GMDS-DT在正常和骨质疏松（Osteoporosis, OP）患者椎体松质骨组织中的表达情况。通过qRT-PCR检测GMDS-DT在不同月龄小鼠体内的表达情况。在骨髓间充质干细胞（Bone mesenchymal stem cells, BMSC）中，利用小干扰RNA（Small interfering RNA, siRNA）及质粒敲低或过表达GMDS-DT，通过Western Blot、qRT-PCR、MTT、克隆形成、EDU、流式细胞术和成骨分化诱导实验检测其对BMSC衰老、增殖、成骨分化及氧化应激产生的影响。通过RNA pull-down和RIP实验分析GMDS-DT与HNRNPA1之间的调控关系。结果：GMDS-DT在OP BMSC中的表达显著下调，小鼠BMSC中GMDS-DT水平随着月龄的增大也明显下降。在BMSC中敲低GMDS-DT减弱细胞抗氧化能力，抑制其增殖和成骨分化，促进BMSC衰老，而过表达能缓解这些影响。机制研究发现，GMDS-DT经HNRNPA1促进BMSC抗氧化酶类基因的表达，增强细胞的增殖和成骨分化能力，延缓细胞衰老。结论：LncRNA GMDS-DT通过其抗氧化作用，调节BMSC的增殖和分化能力，延缓骨质疏松的发生发展。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the role of long non-coding RNA (lncRNA) GMDS-DT in the development of osteoporosis and its potential molecular mechanism. Methods: GMDS-DT expression in normal and osteoporosis (OP) bone tissues was screened and validated by qRT-PCR. GMDS-DT expression in mouse of different months was also detected by qRT-PCR. Small interfering RNA (siRNA) and plasmid were used to knock down or overexpress GMDS-DT in bone mesenchymal stem cells (BMSC). Western Blot, qRT-PCR, MTT, colony forming assay, EDU, Flow cytometry, and osteoblast differentiation test were used to detect its effects on BMSC senescence, proliferation, differentiation and oxidative stress. The interaction between GMDS-DT and HNRNPA1 was explored by RNA pull-down and RIP. Results: GMDS-DT was significantly downexpressed in OP BMSC. The level of GMDS-DT in mouse BMSC also decreased with the increase of age. Knocking down GMDS-DT could reduce cell antioxidant capacity, reduce cell proliferation and differentiation, accelerate cell senescence, while overexpression of GMDS-DT could reverse these effects. Mechanistic studies revealed that GMDS-DT could interact with HNRNPA1, thereby promoting the expression of antioxidant enzyme genes in BMSC, enhancing cell proliferation and osteogenic differentiation, and delaying cell senescence. Conclusion: LncRNA GMDS-DT regulates the proliferation and differentiation of BMSC through its antioxidant effect, delaying the occurrence and development of osteoporosis. |
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