Open AccessA synthetic triterpenoid selectively inhibits the induction of matrix metalloproteinases 1 and 13 by inflammatory cytokines
Author(s) -
Mix Kimberlee S.,
Mengshol John A.,
Benbow Ulrike,
Vincenti Matthew P.,
Sporn Michael B.,
Brinckerhoff Constance E.
Publication year - 2001
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/1529-0131(200105)44:5<1096::aid-anr190>3.0.co;2-6
Subject(s) - matrix metalloproteinase , tumor necrosis factor alpha , proinflammatory cytokine , cytokine , inflammation , interleukin , cancer research , chemistry , microbiology and biotechnology , immunology , biology , biochemistry
Objective To address the effects of a novel synthetic triterpenoid, 2‐cyano‐3,12‐dioxoolean‐1,9‐dien‐28‐oic acid (CDDO), on the induction of matrix metalloproteinases 1 and 13 (MMP‐1, MMP‐13) by inflammatory cytokines. Methods Human chondrosarcoma cells stimulated with inflammatory cytokines (interleukin‐1β [IL‐1β], tumor necrosis factor α) were used to study the effects of CDDO on the induction of MMPs and the invasion of cells through 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 functions at the level of transcription. Additionally, CDDO reduced IL‐1β–mediated 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 osteoarthritis.