摘要
目的观察在不同浓度三碘甲状腺原氨酸环境下人成骨肉瘤MG63细胞株增殖和肿瘤坏死因子相关凋亡诱导配体（TRAIL）及其护骨素（OPG）、护骨素配体（OPGL）的表达,探讨甲亢性骨质疏松症的发病机制。方法用不同浓度T3（0、1.0×10^-12、1.0×10^-10、1.0×10^-8mol/L）分别刺激培养的MG63细胞24 h,MTT比色分析法测定细胞增殖,流式细胞仪检测细胞周期,逆转录PCR（RT-PCR）法检测基因表达情况,免疫细胞化学法检测MG63细胞中TRAIL的表达及分布。结果T3以浓度依赖方式抑制MG63细胞的增殖,并将细胞阻滞于G1期。T3能下调MG63细胞中OPG的表达,上调OPGL和TRAIL的表达。TRAIL免疫反应阳性物质密度高浓度T3组明显高于对照组。结论T3可抑制成骨细胞的增殖,导致成骨细胞中TRAIL和OPGL表达增多,OPG的表达减少。这可能是甲亢性骨质疏松症的重要发病机制之一。
Objective To observe the regulative effects of different concentration of T3 on the proliferation and expressions of osteoprotegerin （OPG）, the ligand of osteoprotegerin （OPGL） and tumor necrosis factor-related apoptosis-inducing ligand （TRAIL）in osteosarcoma MG63 cells, and to study the role of non-physiological concentration of T3 in pathogenesis of hyperthyrodism osteoporosis. Methods The osteoblast proliferation was measured by antigenic MTT eolorimetric analysis. The cell cycle of the cells was determined by flow eytometry. The expressions of OPG, OPGL and TRAIL mRNA were examined by reverse transcriptase（ RT）-PCR, expression and distribution of TRAIL in MG63 cells was investigated by immunohistochemical method. Results T3 could restrain the proliferation of MG63 cells in a dose-dependent manner and could arrest the cell cycle at G1 phase. High concentration of T3 up-regulated the expressions of OPGL and TRAIL but down-regulated OPG expression in the MG63 cells, and the intensity of immunostaining for TRAIL in high concentration of T3 group was stronger than that in control group. Conclusion One of the key pathogenetic factors of hyperthyrodism osteoporosis is that high concentration T3 restrains the proliferation of MG63 cells and leads to the decreasing expression of OPG but the increasing expressions of some bone-resorbing cytokines such as OPGL and TRAIL in osteoblasts, then stimulates osteoclast differentiation and activity, which potentiates bone resorption and bone loss.
出处
《中国骨质疏松杂志》
CAS
CSCD
2009年第6期423-427,共5页
Chinese Journal of Osteoporosis
