The Application of Antioxidant from Chinese Herb in Regulation of Proinflammatory Cytokines and Metalloproteinases in Osteoarthritis
Date Issued
2008
Date
2008
Author(s)
Chen, Moon-Pei
Abstract
Osteoarthritis is one of the major degenerative diseases which affects millions people these days. Due to the tissue specificity, such as low turnover rate and avascular environment, the self-repair of cartilage is considered to be limited. For the intervention of cartilage destruction in OA, inhibition of enzymatic degradation of extracellular matrix (ECM) as well as maintaining the cellular phenotype is one of the major goals of interest. ree radicals, including reactive oxygen speicies (ROS) and reactive nitrogen species (RNS), are the active biochemical compounds that associated with the chronic inflammatory reaction in osteoarthritis. Observation of lipid peroxidation products and nitrated collagen peptide in the serum of patient implicates the role of free radicals in the pathology osteoarthritis. he first part of this study is to use to hydrogen peroxide to provide the oxidative stress and assess the gene expression of chondrocytes cultured within it. Results from real-time PCR reveal that incubated chondrocytes in hydrogen peroxide in either short term or long term did up-regulate the inflammatory gene IL-1 and TNF-α expression in mRNA level. It also triggered the expression of metalloproteinase MMP-1 and MMP-13, which are both crucial enzymes responsible for cartilage destruction in OA. The down-regulation of SOX-9 also implicates the involvement of ROS in the loss of phenotype in osteoarthritic cartilage. The similar gene expression pattern between hydrogen peroxide-stimulated chondrocytes and osteoarthritic chodrocytes provides stronger evidence that link ROS to the pathology of OA. he second part in my study is to use ferulic acid, the natural antioxidant compound from Chinese herb Angelica (Dong-Gui) which is reported to have excellent antioxidant property compared to γ-tocopherol, α-carotene, and ascorbic acid, to retrieve the effects result from excess produced free radical. In our preliminary results, ferulic acid shows low cytotoxicity on chondrocytes according to the WST-1, LDH, and crystal violet assay. Within the safety concentration, pre-treat ferulic acid can down-regulate hydrogen peroxide-induced IL-1, TNF-α, MMP-1 and partially restore SOX-9 gene expression in mRNA level. Post-treatment of ferulic acid also intervened MMP-1, MMP-13 gene expression showing the potential of ferulic acid blocking the unusual catabolic activity that trigger by hydrogen peroxide.urthermore, while HA alone did not do much effect on hydrogen peroxide-treated chondrocytes, ferulic acid containing HA gel showed protective and therapeutic effects by down-regulating IL-1, TNF-α, MMP-1, MMP-13 and up-regulating SOX-9 gene expression in pre-treatment and post-treatment model.The result in this study provided stronger evidence that implicate hydrogen peroxide in the pathology of OA and shows the potential of ferulic acid- containing HA gel in providing extra protective and therapeutic effect in treatment of OA.
Subjects
osteoarthritis
free radical
hydrogen peroxide
hyaluronic acid
ferulic acid
antioxidant
pro-inflammatroy cytokines
Type
thesis
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