Osteoarthritis-related changes in gene expression in knee articular chondrocytes in a rat model of osteoarthritis.

Cartilage destruction in osteoarthritis (OA) results from disturbed chondrocyte metabolism. Here, we used microarrays to show that TGF alpha and CCL2 are simultaneously upregulated in a rat model of OA and cooperate to drive cartilage degradation. The goals of the experiments included here were to a) characterize gene expression in knee joint articular chondrocytes at various stages of development of OA (2 and 8 weeks after surgical induction of OA), and b) to establish trends in gene expression among groups of genes related to the TGF alpha-EGFR axis, over time, in OA. The model chosen to study these results has been previously validated (Appleton, CT et al, 2007, Arthritis Rheum) and used to describe similar gene expression results at a different time point (4 weeks) after induction of OA. The rat model of OA involves surgical destabilization of the knee joint, followed by forced low-intensity mobilization over several weeks; a sham surgery is used as the control (representing a healthy non-OA knee joint) wherein a surgical incision is made but not structural (i.e. ligamentous) modification is made to the joint. Altogether, our data indicate that TGF and CCL2 cooperate to drive cartilage degradation in osteoarthritis.骨关节炎（osteoarthritis, OA）中的软骨破坏由软骨细胞代谢紊乱引发。本研究借助微阵列（microarrays）技术证实，在大鼠骨关节炎模型中，转化生长因子α（TGF alpha）与趋化因子配体2（CCL2）呈现同步上调趋势，并协同驱动软骨降解过程。本研究的实验目标包含两点：其一，明确手术诱导骨关节炎后2周与8周这两个不同病程阶段的膝关节关节软骨细胞的基因表达特征；其二，探究骨关节炎进程中，与转化生长因子α-表皮生长因子受体（TGF alpha-EGFR）轴相关的基因集群的基因表达随时间变化的趋势。本研究所采用的骨关节炎大鼠模型已在既往研究中得到验证（Appleton CT等，2007，Arthritis Rheum），且曾被用于描述骨关节炎诱导后4周这一时间点的相似基因表达结果。该大鼠骨关节炎模型的构建方式为：先实施膝关节手术失稳操作，随后在数周内对大鼠进行强制低强度活动；假手术组作为健康非骨关节炎膝关节的对照，仅做手术切口，未对关节进行结构性（即韧带相关）修饰。综上，本研究数据证实转化生长因子α与趋化因子配体2协同促进骨关节炎中的软骨降解。