%0 Journal Article
%T Pomegranate extract inhibits the interleukin-1¦Â-induced activation of MKK-3, p38¦Á-MAPK and transcription factor RUNX-2 in human osteoarthritis chondrocytes
%A Zafar Rasheed
%A Nahid Akhtar
%A Tariq M Haqqi
%J Arthritis Research & Therapy
%D 2010
%I BioMed Central
%R 10.1186/ar3166
%X Human chondrocytes were derived from OA cartilage by enzymatic digestion, treated with PE and then stimulated with IL-1¦Â. Gene expression of p38-MAPK isoforms was measured by RT-PCR. Western immunoblotting was used to analyze the activation of MAPKs. Immunoprecipitation was used to determine the activation of p38-MAPK isoforms. DNA binding activity of RUNX-2 was determined using a highly sensitive and specific ELISA. Pharmacological studies to elucidate the involved pathways were executed using transfection with siRNAs.Human OA chondrocytes expressed p38-MAPK isoforms p38¦Á, -¦Ã and -¦Ä, but not p38¦Â. IL-1¦Â enhances the phosphorylation of the p38¦Á-MAPK and p38¦Ã-MAPK isoforms but not of p38¦Ä-MAPK isoform in human OA chondrocytes. Activation of p38-MAPK in human OA chondrocytes was preferentially mediated via activation of MKK3. In addition, we also demonstrate that polyphenol rich PE inhibited the IL-1¦Â-induced activation of MKK3, p38¦Á-MAPK isoform and DNA binding activity of the transcription factor RUNX-2.Our results provide an important insight into the molecular basis of the reported cartilage protective and arthritis inhibitory effects of pomegranate extract. These novel pharmacological actions of PE on IL-1¦Â stimulated human OA chondrocytes impart a new suggestion that PE or PE-derived compounds may be developed as MKK and p38-MAPK inhibitors for the treatment of OA and other degenerative/inflammatory diseases.Osteoarthritis (OA), the most common forms of arthritis, is a progressive degenerative joint disease that has a major impact on joint function and the patient's quality of life. This disorder is regulated by proinflammatory cytokines such as IL-1 and TNF-¦Á that can activate a broad array of intracellular signal transduction mechanisms [1]. Of the cytokine- activated pathways, MAP kinases are especially important because they regulate the production of several mediators of inflammation and cartilage damage [2]. Members of the MAP kinase family phosphorylate a
%U http://arthritis-research.com/content/12/5/R195