Triptolide suppresses proinflammatory cytokine-induced matrix metalloproteinase and aggrecanase-1 gene expression in chondrocytes

Biochem Biophys Res Commun. 2005 Feb 4;327(1):320-7. doi: 10.1016/j.bbrc.2004.12.020.

Abstract

A hallmark of rheumatoid- and osteoarthritis (OA) is proinflammatory cytokine-induced degeneration of cartilage collagen and aggrecan by matrix metalloproteinases (MMPs) and aggrecanases (ADAMTS). Effects of the Chinese herb, Tripterygium wilfordii Hook F (TWHF), on cartilage and its anti-arthritic mechanisms are poorly understood. This study investigated the impact of a purified derivative of TWHF, PG490 (triptolide), on cytokine-stimulated expression of the major cartilage damaging proteases, MMP-3, MMP-13, and ADAMTS4. PG490 inhibited cytokine-induced MMP-3, MMP-13 gene expression in primary human OA chondrocytes, bovine chondrocytes, SW1353 cells, and human synovial fibroblasts. Triptolide was effective at low doses and blocked the induction of MMP-13 by IL-1 in human and bovine cartilage explants. TWHF extract and PG490 also suppressed IL-1-, IL-17-, and TNF-alpha-induced expression of ADAMTS-4 in bovine chondrocytes. Thus, PG490 could protect cartilage from MMP- and aggrecanase-driven breakdown. The immunosuppressive, cartilage protective, and anti-inflammatory properties could make PG490 potentially a new therapeutic agent for arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins
  • ADAMTS4 Protein
  • Animals
  • Cartilage / drug effects
  • Cartilage / metabolism
  • Cattle
  • Cells, Cultured
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Collagenases / genetics*
  • Collagenases / metabolism
  • Cytokines / antagonists & inhibitors*
  • Cytokines / pharmacology
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Epoxy Compounds
  • Gene Expression Regulation / drug effects*
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Interleukin-1 / pharmacology
  • Interleukin-17 / pharmacology
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 3 / genetics*
  • Matrix Metalloproteinase 3 / metabolism
  • Matrix Metalloproteinase Inhibitors
  • Metalloendopeptidases / genetics*
  • Phenanthrenes / pharmacology*
  • Plant Extracts / pharmacology
  • Procollagen N-Endopeptidase
  • RNA, Messenger / genetics
  • Tripterygium / chemistry
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Cytokines
  • Diterpenes
  • Epoxy Compounds
  • Interleukin-1
  • Interleukin-17
  • Matrix Metalloproteinase Inhibitors
  • Phenanthrenes
  • Plant Extracts
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • triptolide
  • ADAM Proteins
  • Collagenases
  • MMP13 protein, human
  • Matrix Metalloproteinase 13
  • Metalloendopeptidases
  • Procollagen N-Endopeptidase
  • Matrix Metalloproteinase 3
  • ADAMTS4 Protein
  • ADAMTS4 protein, human