A synthetic triterpenoid selectively inhibits the induction of matrix metalloproteinases 1 and 13 by inflammatory cytokines

Objective. To address the effects of a novel synthetic triterpenoid, 2-cyan o-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), on the induction of matrix m etalloproteinases 1 and 13 (MMP-1, MMP-13) by inflammatory cytokines. Methods. Human chondrosarcoma cells stimulated with inflammatory cytokines (interleukin-1 beta [IL-1 beta], tumor necrosis factor a) were used to stud y the effects of CDDO on the induction of MMPs and the invasion of cells th rough a collagen matrix. Results. CDDO selectively reduced the induction of MMP-1 and MMP-13 at the levels of messenger RNA and protein. Treatment with CDDO prior to cytokine stimulation enhanced this inhibition, and we demonstrated that CDDO functio ns at the level of transcription. Additionally, CDDO reduced IL-1 beta -med iated invasion of cells through a collagen matrix. Conclusion. This study demonstrates that CDDO is a novel inhibitor of MMP-1 and MMP-13 gene expression mediated by inflammatory cytokines. Thus, CDDO may have therapeutic potential for the inhibition of joint degradation in o steoarthritis.