Kósa János P, Balla Bernadett, Speer Gábor, Kiss János, Borsy Adrienn, Podani János, Takács István, Lazáry Aron, Nagy Zsolt, Bácsi Krisztián, Orosz László, Lakatos Péter
1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
Menopause. 2009 Mar-Apr;16(2):367-77. doi: 10.1097/gme.0b013e318188b260.
Menopausal changes influence the growth, differentiation, and metabolism of bone tissue. Hormonal deficiency at the time of menopause results in marked increases in bone resorption and formation, leading to rapid bone loss. The aim of our investigation was to determine genes characterized by significantly changed mRNA expression rates in postmenopausal versus premenopausal nonosteoporotic bone tissue and to describe the interrelationships among these genes using multivariate data analysis.
Ten bone tissue samples from postmenopausal nonosteoporotic women and seven bone tissue samples from premenopausal nonosteoporotic women were examined. The expression differences of 118 selected genes were analyzed in a TaqMan probe-based quantitative reverse transcriptase-polymerase chain reaction system.
The Mann-Whitney U test indicated significant differences in the expression of 29 genes of postmenopausal and premenopausal nonosteoporotic women. Twenty-eight genes, including extracellular matrix molecules and digesting enzymes, genes belonging to the transforming growth factor-beta/bone morphogenic protein pathway, transcription factors, growth factors, and other candidate genes, were significantly up-regulated in postmenopausal women compared with premenopausal women. Only one gene (ENO1) showed down-regulation after menopause. Based on the multiple mRNA expression profiles of 118 genes, postmenopausal and premenopausal states could be differentiated by enhanced postmenopausal gene expression levels using principal components analysis. Canonical variates analysis demonstrated that postmenopausal and premenopausal nonosteoporotic bone tissues can be distinguished by expression analysis of genes controlled via estrogen receptor-alpha and genes coding for extracellular matrix molecules.
The menopausal state of bone tissue has been unambiguously defined by its complex gene transcription pattern. Significant differences observed in the gene expression profiles of estrogen-deficient human bone tissue provide further insight into the process of postmenopausal changes of bone metabolism.
绝经变化会影响骨组织的生长、分化和代谢。绝经时的激素缺乏会导致骨吸收和形成显著增加，从而导致快速的骨质流失。我们研究的目的是确定在绝经后与绝经前非骨质疏松性骨组织中mRNA表达率有显著变化特征的基因，并使用多变量数据分析来描述这些基因之间的相互关系。
对10例绝经后非骨质疏松女性的骨组织样本和7例绝经前非骨质疏松女性的骨组织样本进行检测。在基于TaqMan探针的定量逆转录-聚合酶链反应系统中分析118个选定基因的表达差异。
曼-惠特尼U检验表明，绝经后和绝经前非骨质疏松女性的29个基因表达存在显著差异。与绝经前女性相比，绝经后女性中有28个基因显著上调，包括细胞外基质分子和消化酶、属于转化生长因子-β/骨形态发生蛋白途径的基因、转录因子、生长因子以及其他候选基因。只有一个基因（ENO1）在绝经后表现为下调。基于118个基因的多个mRNA表达谱，使用主成分分析可以通过绝经后基因表达水平的增强来区分绝经后和绝经前状态。典型变量分析表明，绝经后和绝经前非骨质疏松性骨组织可以通过雌激素受体-α调控的基因以及细胞外基质分子编码基因的表达分析来区分。
骨组织的绝经状态已通过其复杂的基因转录模式得到明确界定。在雌激素缺乏的人类骨组织基因表达谱中观察到的显著差异，为绝经后骨代谢变化过程提供了进一步的见解。
