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人类骨髓细胞中主要谱系定义因子的基因表达分析:衰老、性别及年龄相关疾病的影响

Gene expression analysis of major lineage-defining factors in human bone marrow cells: effect of aging, gender, and age-related disorders.

作者信息

Jiang Ying, Mishima Hajime, Sakai Shinsuke, Liu Yin-Kun, Ohyabu Yoshimi, Uemura Toshimasa

机构信息

Nanotechnology Research Institute (NRI), National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.

出版信息

J Orthop Res. 2008 Jul;26(7):910-7. doi: 10.1002/jor.20623.

Abstract

Adult bone marrow cells (BMCs) include two populations:;mesenchymal stem cells (MSCs), which can differentiate into bone, cartilage, and fat; and hematopoietic stem cells (HSCs), which produce all mature blood lineage. To study the effect of aging, gender, and age-related disorders on lineage differentiation, we performed quantitative RT-PCR to examine mRNA expression of the major factors defining BMC lineage, cbfa1 for osteoblasts, ppar-gamma for adipocytes, sox9 for chondrocytes, and rankl for osteoclasts, in bone marrow from 80 healthy subjects and patients (14-79 years old) with two age-related disorders: osteoarthritis (OA) and rheumatoid arthritis (RA). Two apoptosis-related genes, bcl-2 and drak1, were studied. RANKL and PPAR-Gamma levels exhibited a clear positive correlation with age in female patients, but not in males, with a slight age-related decline in CBFa1 transcripts. DRAK1 expression showed an age-associated ascending trend with significantly greater transcripts of RANKL and DRAK1 in females (p < 0.01). Compared with age-matched controls, RA patients exhibited increased RANKL, PPAR-Gamma, and DRAK1 mRNA levels (p < 0.05), and OA showed the higher RANKL and PPAR-Gamma transcripts (p < 0.05). Furthermore, SOX9 and DRAK1 expressions in the RA group were higher than in the OA group (p < 0.05). Our data indicate that aging and age-related disorders affect gene expressions differently, suggesting that in aging, the lineage of bone marrow cells was modified with prominent changes in decreased bone marrow osteoblastogenesis, increased adipogenesis and osteoclastogenesis, while in age-related disorders, marrow adipogenesis and the activity or number of osteoclasts may play an important role in the pathogenesis of arthritic bone loss.

摘要

成人骨髓细胞(BMCs)包括两类细胞群:间充质干细胞(MSCs),可分化为骨、软骨和脂肪;造血干细胞(HSCs),可产生所有成熟的血细胞谱系。为了研究衰老、性别及与年龄相关的疾病对谱系分化的影响,我们进行了定量逆转录聚合酶链反应(RT-PCR),检测了80名健康受试者和患有两种与年龄相关疾病(骨关节炎(OA)和类风湿性关节炎(RA))的患者(14 - 79岁)骨髓中定义BMC谱系的主要因子的mRNA表达,这些因子包括成骨细胞的Cbfa1、脂肪细胞的过氧化物酶体增殖物激活受体γ(ppar-γ)、软骨细胞的Sox9以及破骨细胞的核因子κB受体活化因子配体(rankl)。同时研究了两个与细胞凋亡相关的基因,即bcl-2和死亡相关蛋白激酶1(drak1)。在女性患者中,RANKL和PPAR-γ水平与年龄呈明显正相关,而男性患者则不然,Cbfa1转录本随年龄略有下降。DRAK1表达呈现与年龄相关的上升趋势,女性患者中RANKL和DRAK1的转录本显著增多(p < 0.01)。与年龄匹配的对照组相比,RA患者的RANKL、PPAR-γ和DRAK1 mRNA水平升高(p < 0.05),OA患者的RANKL和PPAR-γ转录本水平更高(p < 0.05)。此外,RA组中SOX9和DRAK1的表达高于OA组(p < 0.05)。我们的数据表明,衰老和与年龄相关的疾病对基因表达的影响不同,这表明在衰老过程中,骨髓细胞谱系发生改变,骨髓成骨显著减少、脂肪生成和破骨细胞生成增加,而在与年龄相关的疾病中,骨髓脂肪生成以及破骨细胞的活性或数量可能在关节炎性骨质流失的发病机制中起重要作用。

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