title: Resveratrol inhibits the IL-1β-induced expression of MMP-13 and IL-6 in human articular chondrocytes via TLR4/MyD88-dependent and -independent signaling cascades.
abstract: The natural polyphenolic compound, resveratrol, has been shown to exhibit anti-osteoarthritic activity. Therefore it is hypothesized that resveratrol may serve as a nutritional supplement to counteract osteoarthritis (OA). However, the mechanisms responsible for these anti-osteoarthritic effects have not yet been fully elucidated. The aim of this study was to determine whether the biological effects of resveratrol against interleukin (IL)-1β‑induced inflammation in human articular chondrocytes involved both Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)-dependent and -independent signaling pathways. Human articular chondrocytes derived from patients with OA were stimulated with IL-1β, and then co-treated with resveratrol. Cell viability was subsequently evaluated by MTS assays, and the concentrations of matrix metalloproteinase (MMP)-13 and the pro-inflammatory factor, IL-6, were detected in culture supernatants using ELISA. The mRNA and protein levels of downstream mediators of TLR4/MyD88-dependent and -independent signaling pathways were also assayed by RT-qPCR and western blot analysis, respectively. Our results revealed that resveratrol prevented the IL-1β-induced reduction in cell viability. Furthermore, stimulation of the chondrocytes with IL-1β resulted in a significant upregulation of TLR4 and downstream targets of both TLR4/MyD88-dependent and -independent signaling pathways that are associated with the synthesis of MMP-13 and IL-6. Correspondingly, IL-1β-induced catabolic and inflammatory responses were effectively reversed by resveratrol. Taken together, these data suggest that resveratrol exerted protective effects against matrix degradation and inflammation in OA-affected chondrocytes by inhibiting both TLR4/MyD88-dependent and -independent signaling pathways. Thus, resveratrol represents a potential treatment for OA and warrants further investigation.
authors.affiliation: Department of Orthopedics, Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Hailun
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Xingyao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
mesh_terms: D000368:Aged; D015415:Biomarkers; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D053583:Interleukin-1beta; D015850:Interleukin-6; D053594:Myeloid Differentiation Factor 88; D013267:Stilbenes; D051197:Toll-Like Receptor 4; D053509:Matrix Metalloproteinase 13; D000077185:Resveratrol