Zhang Fang-Jie, Yu Wen-Bo, Luo Wei, Gao Shu-Guang, Li Yu-Sheng, Lei Guang-Hua
Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China ; Department of Orthopaedics, The First People's Hospital of Nanpin, Nanpin, Fujian 353000, P.R. China.
Exp Ther Med. 2014 Aug;8(2):391-394. doi: 10.3892/etm.2014.1750. Epub 2014 May 29.
Tissue inhibitors of metalloproteinases (TIMPs) regulate the activity of matrix metalloproteinases (MMPs) and enzymes from the a disintegrin and metalloproteinase domain with thrombospondin motifs family in osteoarthritis (OA). Elevated osteopontin (OPN) levels in plasma, synovial fluid and articular cartilage are associated with progressive OA joint damage; however, the role of OPN in the pathological changes of knee OA remains undetermined. The present study was undertaken to examine the effect of OPN on the expression of TIMP-1 and TIMP-2 mRNA in chondrocytes from 16 patients with knee OA. In this study, following the stimulation of human chondrocytes with recombinant human OPN (rhOPN; 100 ng/ml and 1 μg/ml, respectively) for 48 h, MTT assay was used to determine cell viability while the quantitative polymerase chain reaction (PCR) was used to detect the alterations in TIMP-1 and TIMP-2 levels. The results illustrated that neither 100 ng/ml nor 1 μg/ml rhOPN caused cytotoxicity or apoptosis of chondrocytes and that the relative mRNA expression of TIMP-1 and TIMP-2 was significantly increased in the 1 μg/ml rhOPN group compared with that in the control group (P=0.022 and P=0.003, respectively). However, no significant difference in expression was revealed between the 100 ng/ml rhOPN and control groups (P=0.998 and P=0.209, respectively). In conclusion, OPN may have a protective effect against pathological changes in advanced-stage OA.
金属蛋白酶组织抑制剂（TIMPs）在骨关节炎（OA）中调节基质金属蛋白酶（MMPs）以及来自具有血小板反应蛋白基序的解整合素和金属蛋白酶结构域家族的酶的活性。血浆、滑液和关节软骨中骨桥蛋白（OPN）水平升高与OA关节损伤进展相关；然而，OPN在膝关节OA病理变化中的作用仍未明确。本研究旨在检测OPN对16例膝关节OA患者软骨细胞中TIMP-1和TIMP-2 mRNA表达的影响。在本研究中，用重组人OPN（rhOPN；分别为100 ng/ml和1 μg/ml）刺激人软骨细胞48小时后，采用MTT法测定细胞活力，同时用定量聚合酶链反应（PCR）检测TIMP-1和TIMP-2水平的变化。结果表明，100 ng/ml和1 μg/ml的rhOPN均未引起软骨细胞的细胞毒性或凋亡，且与对照组相比，1 μg/ml rhOPN组中TIMP-1和TIMP-2的相对mRNA表达显著增加（分别为P = 0.022和P = 0.003）。然而，100 ng/ml rhOPN组与对照组之间的表达无显著差异（分别为P = 0.998和P = 0.209）。总之，OPN可能对晚期OA的病理变化具有保护作用。
