Department of Orthopaedics, Dongguk University Ilsan Hospital, Goyang, South Korea.
Cell Biol Int. 2011 May;35(5):529-35. doi: 10.1042/CBI20100251.
This study was performed to investigate the expressions of the SOX trio, PTHrP (parathyroid hormone-related peptide) and IHH (Indian hedgehog protein) in OA (osteoarthritis) using surgically induced rat OA model. After 12 weeks, the articular cartilage from the distal femur was harvested. The expressions of the SOX trio, PTHrP and IHH were explored at gene, protein and epigenetic levels by real-time PCR (n = 5), immunohistochemistry (n = 5) and MSP (methylation-specific PCR). The findings from OA cartilage of the right knees were compared with those from the left knees as the control. The gene expressions of SOX-5, -6, -9 decreased by 58, 20 and 40%, respectively, in the OA cartilage, while their respective protein expressions increased. The PTHrP and IHH gene expressions decreased by 75 and 81%, respectively, although their protein expressions increased. Findings from MSP demonstrated increased methylation in the promoter regions of SOX-5 and -9 genes. This study demonstrated that increased methylation in the promoters of these genes may explain the low gene expression in the surgically induced OA model, whereas elevated protein expression is speculated to be from lag effect in the gene-protein expression.
本研究旨在使用手术诱导的大鼠骨关节炎模型研究 SOX 三兄弟、PTHrP（甲状旁腺激素相关肽）和 IHH（印度刺猬蛋白）在骨关节炎中的表达。12 周后，从股骨远端采集关节软骨。通过实时 PCR（n=5）、免疫组织化学（n=5）和 MSP（甲基化特异性 PCR）在基因、蛋白和表观遗传水平上探索 SOX 三兄弟、PTHrP 和 IHH 的表达。将右膝骨关节炎软骨的发现与作为对照的左膝软骨的发现进行比较。OA 软骨中 SOX-5、-6、-9 的基因表达分别下降了 58%、20%和 40%，而其各自的蛋白表达增加。PTHrP 和 IHH 的基因表达分别下降了 75%和 81%，尽管它们的蛋白表达增加。MSP 的结果表明 SOX-5 和 -9 基因启动子区域的甲基化增加。本研究表明，这些基因启动子中增加的甲基化可能解释了手术诱导的 OA 模型中基因表达水平低的现象，而推测蛋白表达升高是由于基因-蛋白表达的滞后效应。
