ABSTRACT

The A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family is gradually being recognized as an important family of mediators that, along with the matrix metalloproteinases (MMPs), control the degradation process in osteoarthritis (OA). The objective of this study was to uncover the detailed alterations of ADAMTS1, ADAMTS2, and ADAMTS5 in the knee joint of OA mice. The OA model was established by anterior cruciate ligament transection (ACLT) on the knee joints of C57BL/6 J mice. The mice showed representative phenotypes of ACLT-induced OA, including obvious deterioration of the cartilage, reductions in the collagen and proteoglycan components in the cartilage matrix of OA mice, and increased inflammation and osteoclast activity. By qPCR, the gene expression levels of Adamts1, −2, and −5 were the top-ranked among Adamts1-5 in cartilage/chondrocytes, osteogenic tissue/osteoblasts, and cortical bone/osteocytes. Moreover, the protein expression levels of ADAMTS1, −2, and −5 were all increased in articular cartilage, the growth plate, and subchondral bone of the knee joint. The results suggest the important roles of ADAMTS1, −2, and −5 in OA disease, which will be helpful in further research on degenerative changes in OA.

摘要

带有血小板反应蛋白基序的整合素和金属蛋白酶（ADAMTS）家族逐渐被认为是重要的介体家族，与基质金属蛋白酶（MMP）一起控制骨关节炎（OA）的降解过程。这项研究的目的是揭示OA小鼠膝关节中ADAMTS1，ADAMTS2和ADAMTS5的详细变化。通过在C57BL / 6 J小鼠的膝关节前交叉韧带横切（ACLT）建立OA模型。小鼠表现出ACLT诱导的OA的代表性表型，包括软骨的明显恶化，OA小鼠软骨基质中胶原蛋白和蛋白聚糖成分的减少以及炎症和破骨细胞活性的增加。通过qPCR，Adamts1，-2和-5的基因表达水平在软骨/软骨细胞，成骨组织/成骨细胞和皮质骨/成骨细胞中，Adamts1-5中排名最高。此外，ADAMTS1，-2和-5的蛋白质​​表达水平在膝关节的关节软骨，生长板和软骨下骨中均增加。结果表明ADAMTS1，-2和-5在OA疾病中的重要作用，这将有助于进一步研究OA的退行性变化。