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| 生骨再造丸对HDAC6调控BMSCs成骨分化的研究 |
| Shenggu Zaizao pills promote osteogenic differentiation of BMSCs by regulation of HDAC6 |
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| DOI：10.3969/j.issn.1006-7108.2026.05.006 |
| 中文关键词: 组蛋白去乙酰化酶6 骨髓间充质干细胞 成骨分化 生骨再造丸 |
| 英文关键词:histone deacetylase 6 bone marrow mesenchymal stem cells osteogenic differentiation Shenggu Zaizao pills |
| 基金项目:国家自然科学基金（82160915）；兰州市科技局项目（2022-3-23）；敦煌医学与转化教育部重点实验室开放课题项目（DHYX24-11） |
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| 中文摘要: |
| 目的 探讨生骨再造丸对糖皮质激素干预下骨髓间充质干细胞（BMSCs）的生物学机制及对组蛋白去乙酰化酶6（histone deacetylase 6, HDAC6）调控BMSCs成骨分化的影响。方法 将BMSCs分为空白组、模型组、模型+HDAC6激动剂组（模型+Theophylline组）、模型+HDAC6抑制剂组（模型+Trichostatin A组）、模型+生骨再造丸含药血清组。制备生骨再造丸含药血清干预BMSCs的成骨分化。通过CCK8检测各组BMSCs的活性；采用茜素红染色评估BMSCs成骨分化能力；RT-qPCR检测Runx2基因水平；Western Blot检测GRα、Runx2的表达；ELISA检测各组中OPN、OCN、BMP、HDAC6的水平。结果 与空白组相比较，模型组细胞活性降低、成骨分化水平下降（P<0.01），GRα、HDAC6蛋白表达上升（P<0.05），Runx2表达下调，OPN、OCN、BMP水平降低（P<0.01）；与模型组比较，HADC6激动剂组细胞活性明显降低、成骨分化水平显著下降（P<0.05），GRα、HDAC6蛋白表达上升（P<0.05），Runx2表达下调，OPN、OCN、BMP水平明显降低（P<0.05）；HDAC6抑制剂组和生骨再造丸含药血清组的细胞活性明显增高、成骨分化水平显著增加（P<0.05），GRα、HDAC6蛋白表达下降（P<0.05），Runx2表达上升，OPN、OCN、BMP水平明显升高（P<0.05）。结论 生骨再造丸能抑制HDAC6活性，促进BMSCs成骨分化，从而有效治疗激素性股骨头坏死。 |
| 英文摘要: |
| Objective To investigate the therapeutic mechanisms of Shenggu Zaizao pills in a glucocorticoid-induced model, focusing on the effects on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) via the regulation of histone deacetylase 6 (HDAC6). Methods BMSCs were divided into a blank group, a model group, a model group+HDAC6 agonist (a model group+Theophylline) group, a model group+HDAC6 inhibitor (a model group+Trichostatin A) group, and a model group+Shenggu Zaizao pills drug-containing serum group. The drug-containing serum of Shenggu Zaizao pills was prepared to interfere with the osteogenic differentiation of BMSCs. The activity of BMSCs in each group was detected using a CCK8 kit. The osteogenic differentiation capacity of BMSCs was determined using Alizarin red staining. Runx2 level was detected using RT-qPCR. Western blotting was used to detect the expressions of GRα and Runx2. The levels of OPN, OCN, BMP and HDAC6 in each group were detected with ELISA. Results Compared to the blank group, the cell activity and osteogenic differentiation level in the model group decreased (P<0.01), the expressions of GRα and HDAC6 proteins increased (P<0.01), the expression of Runx2 decreased, and the contents of OPN, OCN and BMP significantly decreased (P<0.01). Compared to the model group, the cell viability of the HADC6 agonist group decreased significantly, the level of osteogenic differentiation decreased significantly (P<0.05), the expressions of GRα and HDAC6 proteins increased (P<0.05), Runx2 expression decreased, and the contents of OPN, OCN, and BMP decreased significantly (P<0.05). Both the HDAC6 inhibitor and the Shenggu Zaizao pills drug-containing serum significantly enhanced cell viability and the extent of osteogenic differentiation (P<0.01), and the expression of GRα and HDAC6 proteins decreased (P<0.05), while the expression of Runx2 increased, and the contents of OPN, OCN, and BMP significantly increased (P<0.05). Conclusion Shenggu Zaizao pills inhibits the activity of HDAC6, promotes osteogenic differentiation of BMSCs, and thereby effectively treats steroid-induced osteonecrosis of the femoral head. |
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