title: Effect of osteopontin on the mRNA expression of ADAMTS4 and ADAMTS5 in chondrocytes from patients with knee osteoarthritis.
abstract: Previous studies have demonstrated that osteopontin (OPN) levels are elevated in the synovial fluid and articular cartilage, and are associated with the severity of knee osteoarthritis (OA). However, the role of OPN in the pathogenesis of OA has yet to be elucidated. The present study aimed to investigate the effects of OPN on the expression of the aggrecanases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4 and ADAMTS5, in human OA chondrocytes, as they serve a key function in aggrecan degradation. Human OA chondrocytes were obtained from the knees of 16 patients with OA, and subsequently cultured in a monolayer. The chondrocytes were divided into three groups, which included the control (no treatment), N-OPN (treated with 100 ng/ml OPN, the normal circulating OPN concentration) and the H-OPN groups (treated with 1 µg/ml OPN, a high OPN concentration). Reverse transcription-quantitative polymerase chain reaction was performed to quantify the relative mRNA expression levels of ADAMTS4, ADAMTS5 and aggrecan in the chondrocytes. The mRNA expression levels of ADAMTS4 were significantly reduced in the N-OPN and H-OPN groups when compared with the control group (P<0.0001). In addition, the mRNA expression levels of ADAMTS4 were lower in the H-OPN group when compared with the N-OPN group (P<0.001). However, no statistically significant difference was observed in the relative mRNA expression levels of ADAMTS5 among the three groups (P>0.05). Furthermore, the mRNA expression levels of aggrecan were higher in the N-OPN and H-OPN groups when compared with the control group (P<0.0001), and a statistically significant difference was observed between the N-OPN and H-OPN groups with regard to the mRNA expression of aggrecan (P<0.0001). These results demonstrated that OPN may exert a protective effect in human OA chondrocytes against aggrecan degradation by suppressing the expression of ADAMTS4.
authors.affiliation: Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China ; Orthopedics Institute, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Shu-Guang
authors.initials: SG
authors.lastname: Gao
authors.affiliation: Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zeng
authors.affiliation: Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China ; Department of Orthopedics, Linyi People's Hospital, Linyi, Shandong 276001, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Tuo
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Orthopedics, 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 Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China ; Orthopedics Institute, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Guang-Hua
authors.initials: GH
authors.lastname: Lei
keywords: a disintegrin and metalloproteinase with thrombospondin motifs 4; a disintegrin and metalloproteinase with thrombospondin motifs 5; aggrecan; osteoarthritis; osteopontin