CAJ | 학술논문

背景：骨髓间充质干细胞的多向分化能力在骨代谢疾病中发挥重要作用，受激素、细胞因子等多种因素调节。目前骨髓间充质干细胞骨向分化的表观遗传学调控机制尚不明确，组蛋白去乙酰化酶与骨质疏松的关系尚需进一步探讨。 　　目的：建立雌激素缺乏骨质疏松小鼠的实验动物模型，检测骨髓间充质干细胞组蛋白去乙酰化酶1，3，4 mRNA表达水平，探索卵巢切除小鼠骨组织形成障碍的表观遗传学机制。 　　方法：昆明种小鼠30只随机等分为模型组和假手术组。小鼠适应性喂养7 d后，模型组小鼠切除双侧卵巢，造成雌激素缺乏骨质疏松实验动物模型，假手术组小鼠仅切除等量脂肪组织。 　　结果与结论：模型组小鼠股骨骨小梁稀疏或断裂，骨小梁宽度变窄，骨小梁间距变宽，骨小梁占视野面积降低。与假手术组相比，模型组小鼠骨髓间充质干细胞中组蛋白去乙酰化酶3 mRNA表达水平显著降低，组蛋白去乙酰化酶1，4表达水平变化差异无显著性意义。提示雌激素缺乏导致骨髓间充质干细胞去乙酰化状态改变可能是骨形成障碍的重要原因之一。
배경：골수간충질간세포적다향분화능력재골대사질병중발휘중요작용，수격소、세포인자등다충인소조절。목전골수간충질간세포골향분화적표관유전학조공궤제상불명학，조단백거을선화매여골질소송적관계상수진일보탐토。 　　목적：건립자격소결핍골질소송소서적실험동물모형，검측골수간충질간세포조단백거을선화매1，3，4 mRNA표체수평，탐색란소절제소서골조직형성장애적표관유전학궤제。 　　방법：곤명충소서30지수궤등분위모형조화가수술조。소서괄응성위양7 d후，모형조소서절제쌍측란소，조성자격소결핍골질소송실험동물모형，가수술조소서부절제등량지방조직。 　　결과여결론：모형조소서고골골소량희소혹단렬，골소량관도변착，골소량간거변관，골소량점시야면적강저。여가수술조상비，모형조소서골수간충질간세포중조단백거을선화매3 mRNA표체수평현저강저，조단백거을선화매1，4표체수평변화차이무현저성의의。제시자격소결핍도치골수간충질간세포거을선화상태개변가능시골형성장애적중요원인지일。
BACKGROUND:As the multipotent differentiation potential, bone marrow mesenchymal stem cells exert an important role in bone metabolism disorders, which is regulated by a variety of hormones and cytokines. Currently, the epigenetic regulatory mechanisms underlying osteogenic differentiation of bone marrow mesenchymal stem cells are unclear, and association between histone deacetylase (Hdac) and osteoporosis needs to be further explored. OBJECTIVE:To investigate the epigenetic mechanisms of bone formation by analyzing the expression of Hdac1, 3, 4 mRNA profile in bone marrow mesenchymal stem cells isolated from ovariectomized mice. METHODS:A total 30 female healthy Kunming mice were randomly divided into sham group and ovariectomy group. After 7 days of adaptive feeding, mice in the ovariectomized group (n=15) were subject to bilateral ovariectomy;mice in sham group (n=15) were sham-operated. RESULTS AND CONCLUSION:In the ovariectomy group, the trabecular bone of the femur was sparse or broken, the width of trabecular bone was narrowed, the trabecular separation was widened, and the trabecular bone volume was reduced. The level of Hdac3 mRNA was lower in bone marrow mesenchymal stem cells from ovariectomized mice compared with controls, but there was no significance between Hdac1, Hdac4 mRNA expression of the two groups. These findings demonstrate that Hdac might play an important role in bone remodeling in the model of estrogen deficiency-induced osteoporosis.