Dan Yan1, Bingshu He2, Jie Guo3, Shulan Li4, Jun Wang5. 1. Associate Professor, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, China. Conception and design of the study, acquisition and interpretation of data. 2. MS, Department of Orthopedics, Hubei Provincial Women and Children's Hospital, China. Conception and design of the study, acquisition and interpretation of data. 3. MS, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, China. Acquisition of data, critical revision. 4. MS, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, China. Acquisition of data. 5. Associate Professor, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, China. Design of the study, manuscript writing, critical revision, supervised all phases of the study.
Abstract
PURPOSE: In view of the principal role of Toll-like receptor 4 (TLR4) in mediating sterile inflammatory response contributing to osteoarthritis (OA) pathogenesis, we used lipopolysaccharide (LPS), a known TLR4 activator, to clarify whether modulation of TLR4 contributed to the protective actions of intra-articular administration of curcumin in a classical rat OA model surgically induced by anterior cruciate ligament transection (ACLT). METHODS: The rats underwent ACLT and received 50μl of curcumin at the concentration of 1 mg mL-1 and 10 μg LPS by intra-articular injection once a week for 8 weeks. Morphological changes of the cartilage and synovial tissues were observed. Apoptotic chondrocytes were detected using TUNEL assay. The concentrations of IL-1β and TNF-ɑ in synovial fluid were determined using ELISA kits. The mRNA and protein expression levels of TLR4 and NF-κB p65 were detected by real-time PCR and Western blotting, respectively. RESULTS: Intra-articular administration of curcumin significantly improved articular cartilage injury, suppressed synovial inflammation and down-regulated the overexpression of TLR4 and its downstream NF-κB caused by LPS-induced TLR4 activation in rat osteoarthritic knees. CONCLUSION: The data suggested that the inhibition of TLR4 signal might be an important mechanism underlying a protective effect of local curcumin administration on OA.
PURPOSE: In view of the principal role of Toll-like receptor 4 (TLR4) in mediating sterile inflammatory response contributing to osteoarthritis (OA) pathogenesis, we used lipopolysaccharide (LPS), a known TLR4 activator, to clarify whether modulation of TLR4 contributed to the protective actions of intra-articular administration of curcumin in a classical rat OA model surgically induced by anterior cruciate ligament transection (ACLT). METHODS: The rats underwent ACLT and received 50μl of curcumin at the concentration of 1 mg mL-1 and 10 μg LPS by intra-articular injection once a week for 8 weeks. Morphological changes of the cartilage and synovial tissues were observed. Apoptotic chondrocytes were detected using TUNEL assay. The concentrations of IL-1β and TNF-ɑ in synovial fluid were determined using ELISA kits. The mRNA and protein expression levels of TLR4 and NF-κB p65 were detected by real-time PCR and Western blotting, respectively. RESULTS:Intra-articular administration of curcumin significantly improved articular cartilage injury, suppressed synovial inflammation and down-regulated the overexpression of TLR4 and its downstream NF-κB caused by LPS-induced TLR4 activation in rat osteoarthritic knees. CONCLUSION: The data suggested that the inhibition of TLR4 signal might be an important mechanism underlying a protective effect of local curcumin administration on OA.
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