Effect of Theaflavin-3, 3'-digallate on Matrix Metalloproteinases in Mouse Chondrocytes

Matrix metalloproteinases (MMPs) play an important role in cartilage degradation in rheumatoid arthritis (RA) . The inhibition of MMP-3 mRNA expression, in particular, is an interesting therapeutic target in RA. The green tea polyphenol, epigallocatechin-3-gallate (EGCG), is known to inhibit MMP mRNA expression. However, the action of the black tea polyphenol, theaflavin-3, 3'-digallate (TF3), on MMP mRNA expression in chondrocytes is not well understood. The ability for the polyphenols TF3 and EGCG to affect the mRNA expression of MMPs, members of the a disintegrin and metalloproteinase protein family (ADAMs), tissue inhibitors of metalloproteinases (TIMPs) or the 67 kDa laminin receptor (67LR) was tested in interleukin-1 β-stimulated mouse chondrocytes in vitro. Mouse chondrocytes were obtained from neonatal ddy mice. After 1 week, TF3 or EGCG was added to the cultured mouse chondrocytes with or without IL-1 β. TF3 suppressed interleukin-1 β-induced increases in MMP-3, MMP-9 and MMP-13 mRNA expression to an equal or greater degree than EGCG, while ADAM-15 and 67LR mRNA expression did not change significantly. TF3 recovered interleukin-1 β-induced suppression of TIMP-3 mRNA expression. However, ADAM-17 mRNA production was induced by TF3. This study suggests that TF3 may have a stronger effect than EGCG in controlling the degradation of cartilage in the inflamed joint, and has the therapeutic potential to prevent cartilage destruction via inhibition of MMPs.