Su Xin, Liao Er-yuan, Peng Jian, Wu Xian-ping
Institute of Endocrinology & Metabolism, The Second Hospital of Xiangya Medical College, Central South University, Changsha 410011, China.
Zhonghua Nei Ke Za Zhi. 2003 Nov;42(11):800-3.
To observe the regulative effects of 17 beta-estradiol (17 beta-E(2)) and ICI 182780 on the expression of osteoprotegerin (OPG), the ligand of osteoprotegerin (OPGL) and the related cytokines [macrophage colony-stimulating factor (M-CSF), TRAIL and transforming growth factor beta(TGF beta)] in MG63 cells.
The expression of OPG, OPGL, M-CSF, TRAIL and TGF beta mRNA was examined by reverse transcriptase (RT)-PCR. The expression of OPG and OPGL protein was measured with Western blot.
(1) 17 beta-E(2) up-regulated the expression of OPG and TGF beta but down-regulated OPGL, M-CSF and TRAIL expression in MG63 cells. (2) ICI 182780 showed varied transactivating capability when regulating the expression of OPG, OPGL, TRAIL, M-CSF and TGF beta genes in MG63 cells.
(1) One of the key pathogenetic factors of postmenopausal osteoporosis is that estrogen deficiency leads to the decreasing expression of OPG and TGF beta but the increasing expression of some bone-resorbing cytokines such as OPGL, M-CSF and TRAIL in osteoblasts, then stimulation of osteoclast differentiation and activity which potentiates bone resorption and bone loss; (2) ICI 182780 shows partial transactivating activity in osteoblasts, so it should belong to a kind of selective estrogen receptor modulators.
观察17β-雌二醇(17β-E₂)及ICI 182780对人骨肉瘤MG63细胞护骨素(OPG)、护骨素配体(OPGL)及相关细胞因子[巨噬细胞集落刺激因子(M-CSF)、肿瘤坏死因子相关凋亡诱导配体(TRAIL)和转化生长因子β(TGFβ)]表达的调控作用。
采用逆转录聚合酶链反应(RT-PCR)检测OPG、OPGL、M-CSF、TRAIL及TGFβ mRNA的表达,蛋白质免疫印迹法检测OPG及OPGL蛋白表达。
(1)17β-E₂上调MG63细胞OPG及TGFβ表达,下调OPGL、M-CSF及TRAIL表达。(2)ICI 182780在调控MG63细胞OPG、OPGL、TRAIL、M-CSF及TGFβ基因表达时表现出不同的反式激活能力。
(1)绝经后骨质疏松症的关键发病因素之一是雌激素缺乏导致成骨细胞中OPG及TGFβ表达降低,而一些骨吸收相关细胞因子如OPGL、M-CSF及TRAIL表达增加,从而刺激破骨细胞分化及活性增强,促进骨吸收及骨质丢失;(2)ICI 182780在成骨细胞中表现出部分反式激活活性,应属于选择性雌激素受体调节剂。