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Background: The study aims to investigate the expression of SIRT1 in articular cartilage of patients with primary knee osteoarthritis (OA) and its relationship with disease severity. Methods: Cartilage tissue samples were collected from 38 knee OA patients and 9 normal healthy controls and then ascribed to normal, mild, moderate, and severe groups on the basis of the improved Mankin grading system. The expression of SIRT1 in articular cartilage was detected by immunohistochemistry and western blots. The expression of p53 and acetylated p53 (Ac-p53) was also measured by western blots. Results: The mutual comparisons of the SIRT1 expression levels in all groups have statistical significance except the one between the mild and moderate groups. Moreover, western blot results showed that the SIRT1 was decreased and p53/Ac-p53 were increased in the OA group. The average gray level of SIRT1 increases with the improving grade of the improved Mankin grading system scorers. Conclusions: The expression of SIRT1 in articular cartilage is negatively associated with severity of knee OA, indicating that SIRT1 may act as a monitoring indicator for determining development and progression of knee OA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]