Balla Bernadett, Kósa János P, Kiss János, Borsy Adrienn, Podani János, Takács István, Lazáry Aron, Nagy Zsolt, Bácsi Krisztián, Speer Gábor, Orosz László, Lakatos Péter
1st Department of Internal Medicine, Semmelweis University, Korányi S. u. 2/a, Budapest, 1083, Hungary.
Calcif Tissue Int. 2008 Jan;82(1):12-26. doi: 10.1007/s00223-007-9092-3. Epub 2007 Dec 12.
To identify genes that are differently expressed in osteoporotic and non-osteoporotic human bone and to describe the relationships between these genes using multivariate data analysis.
Seven bone tissue samples from postmenopausal osteoporotic patients and 10 bone tissue samples from postmenopausal non-osteoporotic women were examined in our study. Messenger RNA was prepared from each sample and reverse transcribed to cDNA. The expression differences of 87 selected genes were analyzed in a Taqman probe-based quantitative real-time RT-PCR system.
A Mann-Whitney U-test indicated significant differences in the expression of nine genes (p < or = 0.05). Seven of these nine genes-ALPL, COL1A1, MMP2, MMP13, MMP9, PDGFA, NFKB1-were significantly downregulated in the bone tissue of osteoporotic women, while CD36 and TWIST2 were significantly upregulated in osteoporotic patients. Principal components analysis was used to evaluate data structure and the relationship between osteoporotic and non-osteoporotic phenotypes based on the multiple mRNA expression profiles of 78 genes. Canonical variates analysis demonstrated further that osteoporotic and non-osteoporotic tissues can be distinguished by expression analysis of genes coding growth factors/non-collagen matrix molecules, and genes belonging to the canonical TGFB pathway.
Significant differences observed in gene expression profiles of osteoporotic and non-osteoporotic human bone tissues provide further insight into the pathogenesis of this disease. Characterization of the differences between osteoporotic and non-osteoporotic bones by expression profiling will contribute to the development of diagnostic tools in the future.
鉴定在骨质疏松和非骨质疏松的人类骨骼中差异表达的基因，并使用多变量数据分析描述这些基因之间的关系。
在我们的研究中，检测了7例绝经后骨质疏松患者的骨组织样本和10例绝经后非骨质疏松女性的骨组织样本。从每个样本中制备信使核糖核酸（mRNA）并逆转录为互补脱氧核糖核酸（cDNA）。在基于Taqman探针的定量实时逆转录聚合酶链反应（RT-PCR）系统中分析87个选定基因的表达差异。
曼-惠特尼U检验表明9个基因的表达存在显著差异（p≤0.05）。这9个基因中的7个——碱性磷酸酶（ALPL）、Ⅰ型胶原蛋白α1链（COL1A1）、基质金属蛋白酶2（MMP2）、基质金属蛋白酶13（MMP13）、基质金属蛋白酶9（MMP9）、血小板衍生生长因子A（PDGFA）、核因子κB1（NFKB1）——在骨质疏松女性的骨组织中显著下调，而CD36和 Twist相关蛋白2（TWIST2）在骨质疏松患者中显著上调。主成分分析用于评估数据结构以及基于78个基因的多个mRNA表达谱的骨质疏松和非骨质疏松表型之间的关系。典型变量分析进一步表明，通过对编码生长因子/非胶原蛋白基质分子的基因以及属于典型转化生长因子β（TGFB）途径的基因进行表达分析，可以区分骨质疏松和非骨质疏松组织。
在骨质疏松和非骨质疏松人类骨组织的基因表达谱中观察到的显著差异为深入了解该疾病的发病机制提供了进一步的线索。通过表达谱分析表征骨质疏松和非骨质疏松骨骼之间的差异将有助于未来诊断工具的开发。
