title: Effect of osteopontin on TIMP-1 and TIMP-2 mRNA in chondrocytes of human knee osteoarthritisin vitro.
abstract: 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.
authors.affiliation: Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Fang-Jie
authors.initials: FJ
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Wen-Bo
authors.initials: WB
authors.lastname: Yu
authors.affiliation: Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.affiliation: Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China ; Orthopaedics Institute of Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Shu-Guang
authors.initials: SG
authors.lastname: Gao
authors.affiliation: Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China ; Orthopaedics Institute of Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Guang-Hua
authors.initials: GH
authors.lastname: Lei
keywords: chondrocytes; osteoarthritis; osteopontin; tissue inhibitors of metalloproteinase-1; tissue inhibitors of metalloproteinase-2