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绝经后骨质疏松与非骨质疏松人类骨组织中免疫系统相关基因的转录谱分析。

Transcriptional profiling of immune system-related genes in postmenopausal osteoporotic versus non-osteoporotic human bone tissue.

作者信息

Balla Bernadett, Kósa János P, Kiss János, Podani János, Takács István, Lazáry Aron, Nagy Zsolt, Bácsi Krisztián, Speer Gábor, Lakatos Péter

机构信息

1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary.

出版信息

Clin Immunol. 2009 May;131(2):354-9. doi: 10.1016/j.clim.2009.01.004. Epub 2009 Feb 20.

Abstract

The functional interaction between the immune system and bone metabolism has been established at both molecular and cellular levels. We have used non-parametric and multidimensional expression pattern analyses to determine significantly changed mRNA profile of immune system-associated genes in postmenopausal osteoporotic (OP) vs. non-osteoporotic (NOP) bone tissue. Seven bone tissue samples from OP patients and ten bone tissue samples from NOP women were examined in our study. The transcription differences of selected 44 genes were analyzed in Taqman probe-based quantitative real-time RT-PCR system. Mann-Whitney test indicated significantly down-regulated transcription activity of 3 genes (FCGR2A, NFKB1 and SCARA3) in OP bone tissue which have prominent role in (antibody) clearance, phagocytosis, pathogen recognition and inflammatory response. According to the canonical variates analysis results, the groups of postmenopausal OP and NOP women are separable by genes coding for cytokines, co-stimulators and cell surface receptors affected in innate immunity which have high discriminatory power. Based on the complex gene expression patterns in human bone cells, we could distinguish OP and NOP states from an immunological aspect. Our data may provide further insights into the changes of the intersystem crosstalk between the immune and skeletal systems, as well as into the local immune response in the altered microenvironment of OP bone.

摘要

免疫系统与骨代谢之间的功能相互作用已在分子和细胞水平上得到证实。我们使用非参数和多维表达模式分析来确定绝经后骨质疏松症(OP)与非骨质疏松症(NOP)骨组织中免疫系统相关基因的mRNA谱的显著变化。在我们的研究中,检测了7例OP患者的骨组织样本和10例NOP女性的骨组织样本。在基于Taqman探针的定量实时RT-PCR系统中分析了所选44个基因的转录差异。Mann-Whitney检验表明,OP骨组织中3个基因(FCGR2A、NFKB1和SCARA3)的转录活性显著下调,这些基因在(抗体)清除、吞噬作用、病原体识别和炎症反应中起重要作用。根据典型变量分析结果,绝经后OP和NOP女性组可通过编码细胞因子、共刺激分子和先天免疫中受影响的细胞表面受体的基因进行区分,这些基因具有很高的鉴别能力。基于人类骨细胞中复杂的基因表达模式,我们可以从免疫学角度区分OP和NOP状态。我们的数据可能为免疫系统与骨骼系统之间的系统间串扰变化以及OP骨改变的微环境中的局部免疫反应提供进一步的见解。

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