Chubinskaya S, Merrihew C, Cs-Szabo G, Mollenhauer J, McCartney J, Rueger D C, Kuettner K E
Department of Biochemistry, Rush Medical College, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
J Histochem Cytochem. 2000 Feb;48(2):239-50. doi: 10.1177/002215540004800209.
This study demonstrates for the first time that human articular chondrocytes express osteogenic protein-1 (OP-1). OP-1 was originally purified from bone matrix and was shown to induce cartilage and bone formation. Both OP-1 protein and message were present in human normal and osteoarthritic (OA) cartilages. OP-1 mRNA was upregulated in OA cartilage compared with normal adult tissues. However, the level of mature OP-1 protein in the same OA tissues was downregulated, whereas the pro-OP-1 remained high. Moreover, these two forms of OP-1 were localized in an inverted manner. Mature OP-1 was primarily detected in the superficial layer, whereas the pro-form was mostly in the deep layer of cartilage. The presence of pro- and mature OP-1 in extracts of normal and OA cartilages was confirmed by Western blotting. These findings imply that articular chondrocytes continue to express and synthesize OP-1 throughout adulthood. The observed patterns of the distribution of pro- and mature OP-1 also suggest differences in the processing of this molecule by normal and OA chondrocytes and by the cells in the superficial and deep layers. Distinct distribution of OP-1 and its potential activation in deep zones and regions of cloning in OA cartilages may provide clues to the potential involvement of endogenous OP-1 in repair mechanisms. (J Histochem Cytochem 48:239-250, 2000)
本研究首次证明人类关节软骨细胞表达骨形成蛋白-1(OP-1)。OP-1最初是从骨基质中纯化出来的,已显示其可诱导软骨和骨的形成。OP-1蛋白和信息核糖核酸在人类正常和骨关节炎(OA)软骨中均有存在。与正常成人组织相比,OA软骨中的OP-1信使核糖核酸上调。然而,在相同的OA组织中,成熟OP-1蛋白水平下调,而前OP-1水平仍然很高。此外,这两种形式的OP-1以相反的方式定位。成熟OP-1主要在表层检测到,而前体形式大多在软骨深层。通过蛋白质印迹法证实了正常和OA软骨提取物中存在前体和成熟OP-1。这些发现表明关节软骨细胞在整个成年期持续表达和合成OP-1。观察到的前体和成熟OP-1的分布模式也表明正常和OA软骨细胞以及表层和深层细胞对该分子的加工存在差异。OP-1在OA软骨深层区域和克隆区域的独特分布及其潜在激活可能为内源性OP-1参与修复机制提供线索。(《组织化学与细胞化学杂志》48:239 - 250,2000年)