Zonal Gene Expression of Chondrocytes in Osteoarthritic Cartilage
Zonal Gene Expression of Chondrocytes in Osteoarthritic Cartilage
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DOI：
10.1002/art.24036
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发表时间：
2008-12-01
影响因子：
--
通讯作者：
Ikegawa, Shiro
中科院分区：
文献类型：
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作者：
Fukui, Naoshi;Miyamoto, Yoshinari;Ikegawa, Shiro
目标。目的：测定骨关节炎(OA)软骨区软骨细胞的代谢。骨性关节炎软骨取自4例终末期骨性关节炎患者膝关节大体完好区。软骨被分成3个区，并通过定制的专注于软骨细胞相关基因的微阵列来确定各个区的基因表达谱。对于不同区域表达差异显著的基因，通过激光捕获显微切割和实时聚合酶链式反应(PCR)分析，比较不同区域内OA和对照软骨的表达。对某些基因在特定软骨区的表达进行了相关性分析。共有198个基因(与所调查的基因的40%相似)在不同区带之间的表达水平显著不同。通过激光捕获显微切割和实时定量聚合酶链式反应检测了其中26个基因的表达，证实了微阵列分析的有效性。软骨基质基因的表达主要在骨关节炎软骨中增强，在不同区域的表达水平相似，但不同基因之间的表达程度不同。骨相关基因的表达无论在浅层还是深层均有诱导，且在各自区域的表达呈正相关。5个蛋白水解酶基因在浅表区的表达最强，且表达相关，提示其表达存在共同的调控机制(S)。在骨性关节炎软骨中，软骨细胞的代谢活性在不同区域之间存在较大差异。浅层和深层均有特征性变化。
Objective. To determine the chondrocyte metabolism in respective zones of osteoarthritic (OA) cartilage.Methods. OA cartilage was obtained from macroscopically intact areas of 4 knee joints with end-stage OA. The cartilage was divided into 3 zones, and gene expression profiles were determined in the respective zones by a custom-designed microarray that focused on chondrocyte-related genes. For the genes whose expression was significantly different among the zones, the expression was compared between OA and control cartilage in the respective zones by an analysis using laser capture microdissection and real-time polymerase chain reaction (PCR). For some genes, the correlation of expression was investigated in specific cartilage zones.Results. A total of 198 genes (similar to 40% of those investigated) were found to be expressed at significantly different levels among the zones. Expression of 26 of those genes was evaluated by laser capture microdissection and real-time PCR, which confirmed the validity of microarray analysis. The expression of cartilage matrix genes was mostly enhanced in OA cartilage, at similar levels across the zones but at different magnitudes among the genes. The expression of bone-related genes was induced either in the superficial zone or in the deep zone, and positive correlations were found among their expression in the respective zones. The expression of 5 proteinase genes was most enhanced in the superficial zone, where their expression was correlated, suggesting the presence of a common regulatory mechanism(s) for their expression.Conclusion. In OA cartilage, the metabolic activity of chondrocytes differed considerably among zones. Characteristic changes were observed in the superficial and deep zones.