Connor J R, Kumar S, Sathe G, Mooney J, O'Brien S P, Mui P, Murdock P R, Gowen M, Lark M W
Department of Musculoskeletal Diseases, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.
Osteoarthritis Cartilage. 2001 Nov;9(8):727-37. doi: 10.1053/joca.2001.0475.
To characterize the expression pattern of clusterin in adult human normal and osteoarthritic cartilage.
Clusterin mRNA expression in adult human normal and osteoarthritic cartilage was investigated by analysis of cDNA libraries, TaqMan quantitative RT-PCR, microarray and in situ hybridization.
Sequence analysis of ESTs from adult human normal and osteoarthritic cartilage cDNA libraries demonstrated that the abundance of clusterin in these libraries was equivalent to genes which have been more commonly associated with cartilage. To examine tissue distribution, TaqMan Quantitative PCR analysis was performed using RNA from a panel of individual normal tissues. Clusterin was expressed at significant levels in cartilage, brain, liver, and pancreas. The expression of clusterin mRNA was up-regulated in early osteoarthritic vs normal cartilage when analysed by microarray analysis. Using in situ hybridization, chondrocytes of normal cartilage expressed moderate levels of clusterin. Upper mid-zone chondrocytes in cartilage with early stages of osteoarthritic disease expressed high levels of clusterin mRNA. In advanced osteoarthritic cartilage, the overall expression of clusterin was reduced.
The induction of clusterin has been associated with a variety of disease states where it appears to provide a cytoprotective effect. The increased expression of clusterin mRNA in the early stages of osteoarthritis (OA) may reflect an attempt by the chondrocytes to protect and repair the tissue. In contrast, the decrease in clusterin mRNA in the advanced osteoarthritic cartilage accompanies the final degenerative stages of the disease. An understanding of the expression of clusterin in osteoarthritis may allow consideration of this protein as a marker for cartilage changes in this chronic degenerative condition.
明确簇集素在成人正常及骨关节炎软骨中的表达模式。
通过对cDNA文库的分析、TaqMan定量逆转录聚合酶链反应（RT-PCR）、微阵列分析及原位杂交，研究成人正常及骨关节炎软骨中簇集素mRNA的表达情况。
对成人正常及骨关节炎软骨cDNA文库中的EST进行序列分析表明，这些文库中簇集素的丰度与那些更常与软骨相关的基因相当。为检测组织分布，使用来自一组个体正常组织的RNA进行TaqMan定量PCR分析。簇集素在软骨、脑、肝和胰腺中大量表达。通过微阵列分析发现，与正常软骨相比，骨关节炎早期软骨中簇集素mRNA的表达上调。利用原位杂交技术，正常软骨的软骨细胞表达中等水平的簇集素。骨关节炎早期软骨的上中区软骨细胞表达高水平的簇集素mRNA。在晚期骨关节炎软骨中，簇集素的整体表达降低。
簇集素的诱导与多种疾病状态相关，在这些疾病状态中它似乎发挥细胞保护作用。骨关节炎（OA）早期簇集素mRNA表达增加可能反映软骨细胞保护和修复组织的尝试。相反，晚期骨关节炎软骨中簇集素mRNA的减少伴随着疾病的最终退变阶段。了解簇集素在骨关节炎中的表达情况可能有助于将该蛋白视为这种慢性退行性疾病中软骨变化的标志物。
