Comparative effects of 2 antioxidants, selenomethionine and epigallocatechin-gallate, on catabolic and anabolic gene expression of articular chondrocytes.

Abstract

OBJECTIVE . To determine the effects of selenomethionine (Se-met) and epigallocatechin-gallate (EGCg) on gene expression, activation of mitogen-activating kinases, and DNA binding of nuclear factor-kappaB (NF-kappaB) and apolipoprotein-1 (AP-1) in articular chondrocytes. METHODS Chondrocytes, cultured in low-oxygen tension, were pretreated with L-selenomethionine or EGCg for 24 h, followed by interleukin 1 (IL-1beta) for 1 h (nuclear and cytoplasmic extracts) or 24 h (RNA extraction). Reverse transcription-polymerase chain reaction was performed to determine mRNA levels of matrix metalloproteinases (MMP-1, -3, -13), aggrecanases (-1, -2), IL-1beta, inducible nitric oxide synthase, cyclooxygenases (-1, -2), type II collagen and aggrecan, and transforming growth factor-beta (TGF-beta1, -2, -3) and their receptors I and II. Activity of mitogen-activating protein kinases (MAPK) was assayed by Western blot and AP-1/NF-kB DNA binding by electrophoretic mobility shift assay. RESULTS Pretreatment with 0.5 microM Se-met prevented IL-1beta-induced MMP-1 and aggrecanase-1 expression, and reduced the cytokine inhibitory effect on type II collagen, aggrecan core protein, and TGF-beta receptor II (TGF-betaRII) mRNA levels. EGCg was more efficient in modulating the effects of IL-1beta on the genes studied. Whereas EGCg inhibited the IL-1beta-activated MAPK, NF-kappaB, and AP-1, Se-met stimulated that signaling pathway. This could account for the differential effects exerted by these antioxidants on chondrocytes. CONCLUSION Our data provide insights into the mechanisms whereby ECGg and selenium modulate chondrocyte metabolism. Despite their differential mechanisms of action, the 2 compounds may exert global beneficial effects on articular cartilage.

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@article{Andriamanalijaona2005ComparativeEO, title={Comparative effects of 2 antioxidants, selenomethionine and epigallocatechin-gallate, on catabolic and anabolic gene expression of articular chondrocytes.}, author={Rina Andriamanalijaona and Madeleine Kypriotou and Catherine Baug{\'e} and Emmanuelle Renard and Florence Legendre and Maha Raoudi and Karim Boumediene and Hugues Gatto and Patricia Monginoux and Jean-Pierre Pujol}, journal={The Journal of rheumatology}, year={2005}, volume={32 10}, pages={1958-67} }