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目的 研究 1, 25 二羟维生素D3 [ 1α, 25 (OH)2D3 ]对人成骨细胞基质金属蛋白酶(MMP) 1、MMP 2、膜型基质金属蛋白酶 1 (MT1 MMP)、基质金属蛋白酶抑制因子 1 (TIMP 1 )的影响,探讨 1α, 25(OH)2D3 调节骨代谢作用机制。方法 人成骨细胞用 1α, 25 (OH)2D3 干预。Western杂交检测MT1 MMP蛋白质表达。MMP 1、MMP 2、TIMP 1的分泌及MMP 2的活性用ELISA检测。Northern杂交检测维生素D受体、MT1 MMPmRNA表达。结果 1α, 25 (OH)2D3 对人成骨细胞MMP 1、MMP 2、TIMP 1表达无影响, 10-10 ~ 10-8 mol/L 1α, 25 (OH)2D3 干预诱导成骨细胞MT1 MMP表达呈剂量依赖性 (P值均 <0 05);促进MMP 2激活呈剂量依赖性 [MMP 2活性分别为(42 3 ± 8 6)、(64 4 ±11 4)、(93 5 ±9 9)μg/L, P值均<0 05]。结论 由于MT1 MMP在骨吸收过程中起着关键作用, 1α, 25(OH)2D3 可通过诱导成骨细胞MT1 MMP表达刺激骨吸收。
Objective To investigate the effects of 1, 25 dihydroxy vitamin D3 [1α, 25 (OH) 2D3] on the expression of matrix metalloproteinase 1 (MMP1), MMP2, MT1 MMP and matrix metalloproteinase inhibitor 1 (TIMP-1), to explore the mechanism of 1α, 25 (OH) 2D3 regulating bone metabolism. Methods Human osteoblasts were treated with 1α, 25 (OH) 2D3. Western blot was used to detect MT1 MMP protein expression. The secretion of MMP 1, MMP 2, TIMP 1 and the activity of MMP 2 were detected by ELISA. Northern blotting was used to detect the expression of vitamin D receptor and MT1 MMP mRNA. Results 1α, 25 (OH) 2D3 had no effect on the expression of MMP 1, MMP 2 and TIMP 1 in human osteoblasts. The expression of MT1 MMP in osteoblasts induced by 10-10 ~ 10 -8 mol / L 1α, 25 (OH) (P <0.05). The promotion of MMP-2 activation in a dose-dependent manner [MMP 2 activity was (42 3 ± 8 6), (64 4 ± 11 4), (93 5 ± 9 9) μg / L, all P <0 05]. Conclusion MT1 MMP plays a key role in bone resorption. 1α, 25 (OH) 2D3 can stimulate bone resorption by inducing MT1 MMP expression in osteoblasts.