Regional differences in chondrocyte metabolism in Osteoarthritis

Regional differences in chondrocyte metabolism in Osteoarthritis
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DOI:
10.1002/art.23175
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发表时间:
2008-01-01
影响因子:
--
通讯作者:
Ochi, Takahiro
Ochi, Takahiro
中科院分区:
其他
文献类型:
--
作者:
Fukui, Naoshi;Ikeda, Yasuko;Ochi, Takahiro

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Objective.研究骨关节炎(OA)软骨细胞代谢活性的变化,并考虑OA软骨退变的区域性差异和程度。OA软骨从具有终末期OA的膝关节获得,在宏观上完整的区域和具有不同程度的软骨退化的区域。对照软骨从年龄匹配的供体获得。采用激光捕获显微切割技术,将软骨样品分为浅、中、深三个区域,并定量比较OA和对照软骨各区域的基因表达。在OA软骨中,基因表达随部位变化显著。软骨基质基因的表达在大体上完整的区域中高度增强,但在退变区域中增强不太明显,尤其是在上部区域。相反,在这些区域中,III型胶原和纤连蛋白的表达最增强,表明软骨细胞在那里经历了表型变化。在OA软骨中,软骨基质基因的表达与SOX 9的表达显著相关,但与SOX 5或SOX 6的表达无关。在OA软骨中,III型胶原和纤连蛋白的表达之间的相关性最强,表明它们的表达之间存在一定的联系。本研究结果揭示了OA软骨中软骨细胞代谢变化的全面视图。基因表达谱的变化在退变软骨的上部区域最为明显。该区域基因表达的改变可能与OA相关的软骨基质丢失有关。
Objective. To determine the change in metabolic activity of chondrocytes in osteoarthritic (OA) cartilage, considering regional difference and degree of cartilage degeneration.Methods. OA cartilage was obtained from knee joints with end-stage OA, at both macroscopically intact areas and areas with various degrees of cartilage degeneration. Control cartilage was obtained from age-matched donors. Using laser capture microdissection, cartilage samples were separated into superficial, middle, and deep zones, and gene expression was compared quantitatively in the respective zones between OA and control cartilage.Results. In OA cartilage, gene expression changed markedly with the site. The expression of cartilage matrix genes was highly enhanced in macroscopically intact areas, but the enhancement was less obvious in the degenerated areas, especially in the upper regions. In contrast, in those regions, the expression of type III collagen and fibronectin was most enhanced, suggesting that chondrocytes underwent a phenotypic change there. Within OA cartilage, the expression of cartilage matrix genes was significantly correlated with SOX9 expression, but not with SOX5 or SOX6 expression. In OA cartilage, the strongest correlation was observed between the expression of type III collagen and fibronectin, suggesting the presence of a certain link(s) between their expression.Conclusion. The results of this study revealed a comprehensive view of the metabolic change of the chondrocytes in OA cartilage. The change of gene expression profile was most obvious in the upper region of the degenerated cartilage. The altered gene expression at that region may be responsible for the loss of cartilage matrix associated with OA.