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| 骨细胞程序性坏死上调Biglycan促进PMOP破骨细胞活化的机制 |
| Mechanism of necroptosis of osteocytes in up-regulating biglycan to promote the activation of osteoclasts in postmenopausal osteoporosis |
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| DOI：10.3969/j.issn.1006-7108.2025.01.002 |
| 中文关键词: 绝经后骨质疏松症 骨细胞 程序性坏死 双糖链蛋白多糖 Toll样受体4 破骨细胞 |
| 英文关键词:postmenopausal osteoporosis osteocyte necroptosis biglycan toll-like receptor 4 osteoclasts |
| 基金项目:海南省重点研发项目（ZDYF2021SHFZ084）；海南医学院第一附属医院2023年度青年培育基金项目(HYYFYPY202309) |
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| 中文摘要: |
| 目的 收集临床的绝经后骨质疏松症(postmenopausal osteoporosis，PMOP)标本，检测双糖链蛋白多糖（Biglycan）与Toll样受体4（toll-like receptor 4，TLR4）的表达情况和表达部位，并明确骨细胞程序性坏死上调Biglycan与破骨细胞TLR4表达的相关性。方法 运用H&E染色和TRAP染色观察正常组、骨质疏松组和重度骨质疏松组的骨细胞和破骨细胞的形态变化；应用免疫组织化学染色、免疫荧光染色和Western blot等方法检测各组间Biglycan与TLR4的表达情况和部位，并通过相关性分析明确骨细胞程序性坏死上调Biglycan与破骨细胞TLR4表达是否存在关联。结果 ①各分组间临床基本资料中的年龄、绝经年龄、身高和体重之间无明显差异；而随着PMOP的进展，患者的骨密度T值逐渐下降，且与正常组间的差异明显。②H&E染色和TRAP染色结果提示，PMOP患者破骨细胞的活化与骨细胞程序性坏死相关。③Western blot检测结果提示PMOP患者的Biglycan和TLR4蛋白的表达发生上调。④免疫荧光染色和免疫组织化学染色结果提示PMOP患者骨细胞中的Biglycan和破骨细胞表面的TLR4表达上调，且Biglycan的表达阳性率与TLR4蛋白表达阳性个数呈正相关，其相关系数在免疫组化染色和免疫荧光染色中分别为0.9038与0.8672。结论 在PMOP的进展过程中，损伤相关分子Biglycan是促进破骨细胞活化的重要因子之一，干预Biglycan/TLR4可能是有效抑制PMOP进展的重要方式之一。 |
| 英文摘要: |
| Objective To detect the expressions of biglycan and TLR4 in patients with postmenopausal osteoporosis (PMOP), and to clarify the correlation between the up-regulation of biglycan by necroptosis of osteoblasts and the expression of TLR4 in osteoclasts. Methods H&E staining and TRAP staining were used to observe the morphological changes of osteocytes and osteoclasts in the normal, osteoporosis, and severe osteoporosis group. Immunohistochemical staining, immunofluorescence staining, and Western blotting were applied to detect the expressions and sites of biglycan and TLR4 in all the groups. The correlation analysis was performed to clarify whether there was an association between up-regulation of biglycan in necroptosis of osteocytes and TLR4 expression in osteoclasts. Results (1) There were no significant differences in age, age at menopause, height, and weight in the basic clinical data among the subgroups. However, with the progression of PMOP, the T value of BMD of the patients gradually decreased, and its difference with the normal group was significant. (2) The results of H&E staining and TRAP staining suggested that the activation of osteoclasts in patients with PMOP was associated with necroptosis of osteocytes. (3) The results of Western blotting suggested that the expressions of biglycan and TLR4 proteins were up-regulated in PMOP patients. (4) The results of immunofluorescence staining and immunohistochemistry staining suggested that the expressions of biglycan in osteocytes and TLR4 on the surface of osteoclasts were up-regulated in PMOP patients. The positive rate of biglycan and the number of positive TLR4 protein expression were positively correlated. The correlation coefficients were 0.9038 and 0.8672 in immunohistochemical staining and immunofluorescence staining, respectively. Conclusion During the progression of PMOP, biglycan is one of the important factors that promote the activation of osteoclasts, Intervention with biglycan/ TLR4 may be one of the important ways to effectively inhibit the progression of PMOP. |
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