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Cordycepin modulates inflammatory and catabolic gene expression in interleukin-1beta-induced human chondrocytes from advanced-stage osteoarthritis: an in vitro study.

ABSTRACT: Cordycepin is widely used as for its various pharmacological activities, such as anti-inflammation, anti-angiogenesis, anti-aging, anti-tumor and anti-proliferation. However, the precise role of cordycepin on chondrocytes is not clear. In the present study, we examined the inhibitory effects of cordycepin on interleukin-1 beta (IL-1?)-induced glycosaminoglycan (GAG) release, nitric oxide production as well as gene expressions of inflammatory and catabolic mediators in human cartilage and chondrocytes. Cartilage explants and human chondrocytes were cultured in the absence or in the presence of IL-1? (10 ng/ml) and with or without cordycepin (5-100 ?M). GAG content in the cartilage explants was measured by using the dimethylmethylene blue method and Safranin O staining. Nitric oxide level was determined by Griess reaction. Expressions of MMP-1, MMP-13, cathepsin K, cathepsin S, ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs-4) and ADAMTS-5, inducible nitric oxide synthase (iNOS) and cyclooxgenase-2 (COX-2) were evaluated by real-time quantitative PCR. We found that cordycepin suppressed IL-1?-stimulated GAG release. Gene expressions of catabolic enzymes, including MMP-1, MMP-13, cathepsin K, cathepsin S, ADAMTS-4 and ADAMTS-5, were decreased by cordycepin in a dose-dependent manner. In addition, cordycepin inhibited IL-1?-induced COX-2 and iNOS expression at the transcript level as well as blocked NO production. Our results suggest that cordycepin may possess chondroprotective effect by preventing cartilage denegation and interfering inflammatory response in the pathogenesis of OA.

SUBMITTER: Hu P

PROVIDER: S-EPMC4230148 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Cordycepin modulates inflammatory and catabolic gene expression in interleukin-1beta-induced human chondrocytes from advanced-stage osteoarthritis: an in vitro study.

Hu Pengfei P Chen Weiping W Bao Jiapeng J Jiang Lifeng L Wu Lidong L

International journal of clinical and experimental pathology 20140915 10

Cordycepin is widely used as for its various pharmacological activities, such as anti-inflammation, anti-angiogenesis, anti-aging, anti-tumor and anti-proliferation. However, the precise role of cordycepin on chondrocytes is not clear. In the present study, we examined the inhibitory effects of cordycepin on interleukin-1 beta (IL-1β)-induced glycosaminoglycan (GAG) release, nitric oxide production as well as gene expressions of inflammatory and catabolic mediators in human cartilage and chondro ...[more]

PMID: 25400736

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Project description:Epigallocatechin-3-gallate (EGCG) is a bioactive polyphenol of green tea and exerts potent anti-inflammatory effects by inhibiting signaling events and gene expression. Interleukin-1beta (IL-1?) is the principal cytokine linked to cartilage degradation in osteoarthritis (OA). The objective of this study was to evaluate the global effect of EGCG on IL-1?-induced expression of proteins associated with OA pathogenesis in human chondrocytes.Primary OA chondrocytes were pretreated with EGCG (10 to 100 uM) and then stimulated with IL-1? (5 ng/ml) for 24 hours. Culture supernatants were incubated with cytokine antibody arrays and immunoreactive proteins (80 proteins) were visualized by enhanced chemiluminiscence. Effect of EGCG on IL-1?-induced expression of 18 selected genes was verified by Real time-PCR and effect on IL-6, IL-8 and tumor necrosis factor-alpha (TNF-?) production was determined using specific ELISAs. Western immunoblotting was used to analyze the effect of EGCG on the interleukin-1 receptor-associated kinase 1 (IRAK-1) and TNF receptor-associated factor 6 (TRAF-6) proteins in IL-1?-stimulated chondrocytes. The role of nuclear factor kappa-B (NF-?B) and mitogen activated protein kinases (MAPKs) in the regulation of selected genes and the mechanism involved in EGCG mediated modulation of these genes was determined by using specific inhibitors for NF- ?B (MG132) and MAPKs (p38-MAPK, SB202190; JNK-MAPK, SP600125, ERK-MAPK, PD98059).Out of 80 proteins present on the array, constitutive expression of 14% proteins was altered by EGCG treatment. No significant stimulatory effect was observed on the proteins associated with cartilage anabolic response. Stimulation with IL-1? enhanced the expression of 29 proteins. Expression of all 29 proteins up-regulated by IL-1? was found to be suppressed by EGCG. EGCG also inhibited the expression of the signaling intermediate TRAF-6 at 50 and 100 uM concentrations (P < 0.05). Our results identified several new targets of EGCG, including epithelial neutrophil activating peptide-78 (ENA-78), granulocyte macrophage colony stimulation factor (GM-CSF), growth- related oncogene (GRO), GRO-?, IL-6, IL-8, monocyte chemotactic protein-1 (MCP-1), MCP-3, macrophage inflammatory protein-1beta (MIP-1?), granulocyte chemotactic protein-2 (GCP-2), MIP-3alpha, interferon-gamma-inducible protein-10 (IP-10), nucleosome assembly protein-2 (NAP-2) and leukemia inhibitory factor (LIF). The inhibitory effects of EGCG were mainly mediated by inhibiting the activation of NF-?B and c-Jun N-terminal Kinase (JNK)-MAPK in human chondrocytes.Our results suggest that the potential of EGCG in OA treatment/prevention may be related to its ability to globally suppress the inflammatory response in human chondrocytes. These results identify additional new targets of EGCG and advocate that EGCG may be a potent chondroprotective agent in OA.

Dataset Information

Cordycepin modulates inflammatory and catabolic gene expression in interleukin-1beta-induced human chondrocytes from advanced-stage osteoarthritis: an in vitro study.

Publications

Cordycepin modulates inflammatory and catabolic gene expression in interleukin-1beta-induced human chondrocytes from advanced-stage osteoarthritis: an in vitro study.

Similar Datasets

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