Otsuki Shuhei, Taniguchi Noboru, Grogan Shawn P, D'Lima Darryl, Kinoshita Mitsuo, Lotz Martin
Division of Arthritis Research, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Arthritis Res Ther. 2008;10(3):R61. doi: 10.1186/ar2432. Epub 2008 May 28.
Changes in sulfation of cartilage glycosaminoglycans as mediated by sulfatases can regulate growth factor signaling. The aim of this study was to analyze expression patterns of recently identified extracellular sulfatases Sulf-1 and Sulf-2 in articular cartilage and chondrocytes.
Sulf-1 and Sulf-2 expressions in human articular cartilage from normal donors and patients with osteoarthritis (OA) and in normal and aged mouse joints were analyzed by real-time polymerase chain reaction, immunohistochemistry, and Western blotting.
In normal articular cartilage, Sulf-1 and Sulf-2 mRNAs and proteins were expressed predominantly in the superficial zone. OA cartilage showed significantly higher Sulf-1 and Sulf-2 mRNA expression as compared with normal human articular cartilage. Sulf protein expression in OA cartilage was prominent in the cell clusters. Western blotting revealed a profound increase in Sulf protein levels in human OA cartilage. In normal mouse joints, Sulf expression was similar to human cartilage, and with increasing age, there was a marked upregulation of Sulf.
The results show low levels of Sulf expression, restricted to the superficial zone in normal articular cartilage. Sulf mRNA and protein levels are increased in aging and OA cartilage. This increased Sulf expression may change the sulfation patterns of heparan sulfate proteoglycans and growth factor activities and thus contribute to abnormal chondrocyte activation and cartilage degradation in OA.
硫酸酯酶介导的软骨糖胺聚糖硫酸化变化可调节生长因子信号传导。本研究的目的是分析最近鉴定出的细胞外硫酸酯酶Sulf-1和Sulf-2在关节软骨和软骨细胞中的表达模式。
通过实时聚合酶链反应、免疫组织化学和蛋白质印迹法分析正常供体和骨关节炎(OA)患者的人关节软骨以及正常和老龄小鼠关节中Sulf-1和Sulf-2的表达。
在正常关节软骨中,Sulf-1和Sulf-2的mRNA和蛋白主要在表层表达。与正常人关节软骨相比,OA软骨中Sulf-1和Sulf-2的mRNA表达显著更高。OA软骨中的Sulf蛋白表达在细胞簇中很突出。蛋白质印迹显示人OA软骨中Sulf蛋白水平显著增加。在正常小鼠关节中,Sulf的表达与人类软骨相似,并且随着年龄的增长,Sulf有明显上调。
结果表明,在正常关节软骨中,Sulf表达水平较低,且局限于表层。在衰老和OA软骨中,Sulf的mRNA和蛋白水平增加。这种Sulf表达的增加可能会改变硫酸乙酰肝素蛋白聚糖的硫酸化模式和生长因子活性,从而导致OA中软骨细胞异常激活和软骨降解。