| 王海龙,李龙,廖静,等.miR-106b-5p靶向调控WAC参与骨质疏松发生.骨科,2026,17(4): 366-376. |
| miR-106b-5p靶向调控WAC参与骨质疏松发生 |
| Targeted regulation of WAC by miR-106b-5p is involved in osteoporosis |
| 投稿时间：2025-12-06 |
| DOI：10.3969/j.issn.1674-8573.2026.04.011 |
| 中文关键词: 骨质疏松 miR-106b-5p 含WW结构域卷曲螺旋衔接蛋白 自噬 |
| 英文关键词: Osteoporosis miR-106b-5p WW domain-containing adaptor with coiled-coil Autophagy |
| 基金项目:新疆维吾尔自治区自然科学基金（2022D01A138） |
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| 中文摘要: |
| 目的 探讨miR-106b-5p在骨质疏松中调控程序性细胞死亡（programmed cell death，PCD）通路的机制。方法 首先通过生物信息学分析GSE56815与GSE201543数据集，筛选差异表达基因并评估PCD通路活性，同时预测并验证miR-106b-5p的靶基因。其次，收集骨质疏松与非骨质疏松患者的临床髋关节组织，检测miR-106b-5p及其靶基因和相关蛋白的表达差异。在体外细胞实验中，使用肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）诱导骨髓间充质干细胞（bone marrow mesenchymal stem cells，BMSCs）模拟炎症微环境，通过转染miR-106b-5p模拟物或抑制剂，评估其对细胞学功能及自噬的调控。最后，构建卵巢切除（ovariectomized，OVX）大鼠体内动物模型，经静脉注射miR-106b-5p抑制剂以评估其对骨微结构及分子表达的干预效果。结果 生物信息学分析显示，骨质疏松中自噬等PCD通路受抑，miR-106b-5p显著上调，并直接靶向抑制自噬关键基因，即含WW结构域卷曲螺旋衔接蛋白（WW domain-containing adaptor with coiled-coil，WAC）。临床组织分析进一步证实，骨质疏松患者髋关节组织中miR-106b-5p和自噬接头蛋白（p62）水平显著升高，而WAC及成骨/自噬相关标志物表达显著下降。体外细胞实验表明，抑制miR-106b-5p可显著逆转TNF-α诱导的BMSCs活力下降与凋亡，恢复WAC表达并促进自噬。体内动物模型分析揭示，miR-106b-5p抑制剂能显著改善OVX大鼠的骨小梁微结构破坏，并在活体组织水平逆转WAC及成骨/自噬相关蛋白的异常表达。结论 本研究揭示miR-106b-5p通过抑制自噬关键基因WAC，削弱自噬并损害成骨，为骨质疏松提供新的治疗靶点。 |
| 英文摘要: |
| Objective To explore the contribution of miR-106b-5p to programmed cell death (PCD) pathways in osteoporosis. Methods First, bioinformatics analysis of transcriptomic datasets (GSE56815 and GSE201543) was performed to identify differentially expressed genes, evaluate PCD pathway activities, and predict miR-106b-5p targets. Second, clinical hip joint tissues from osteoporosis and non-osteoporosis patients were collected to assess the expression of miR-106b-5p, its target, and related markers. In vitro, bone marrow mesenchymal stem cells (BMSCs) treated with tumor necrosis factor-α (TNF-α) were transfected with miR-106b-5p mimic or inhibitor to evaluate their effects on cellular functions and autophagic flux. Finally, an in vivo ovariectomized (OVX) rat model was established and treated with a miR-106b-5p inhibitor to evaluate its therapeutic effects on bone microstructure and molecular expression. Results Bioinformatics analysis revealed that autophagy and other PCD pathways were significantly inhibited in osteoporosis, with miR-106b-5p being significantly upregulated and directly targeting the key autophagy gene, WW domain-containing adaptor with coiled-coil (WAC). Clinical tissue analysis confirmed that miR-106b-5p and p62 levels were significantly elevated in osteoporotic hip tissues, whereas WAC and osteogenic/autophagic markers were markedly downregulated. In vitro experiments demonstrated that inhibition of miR-106b-5p significantly reversed TNF-α-induced apoptosis and viability reduction in BMSCs, restoring WAC expression and promoting autophagic flux. In vivo animal model analysis showed that the miR-106b-5p inhibitor significantly improved trabecular microstructural damage in OVX rats and reversed the abnormal expression of WAC and related proteins. Conclusion This study identifies miR-106b-5p as a suppressor of autophagy via targeting WAC in osteoporosis. Targeted inhibition of miR-106b-5p represents a potential therapeutic avenue to enhance osteogenesis and bone integrity. |
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