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Anti-arthritic effects of chlorogenic acid in interleukin-1β-induced rabbit chondrocytes and a rabbit osteoarthritis model.

Abstract
Cartilage degradation is one of the pathological changes of osteoarthritis (OA), and accumulating evidence suggests an excess of matrix metalloproteinases (MMPs) plays a role in this cartilage breakdown. Here, we investigated the effects of chlorogenic acid (CGA) on the mRNA and protein expression of MMPs in interleukin (IL)-1β-induced rabbit chondrocytes and evaluated the in vivo effects of CGA in experimental OA induced by anterior cruciate ligament transection (ACLT) in rabbits. Using quantitative real-time PCR and ELISA to investigate the expression levels of MMP-1, MMP-3, MMP-13, and tissue inhibitors of metalloproteinase-1(TIMP-1) in IL-1β-induced rabbit chondrocytes, we showed that CGA inhibits the expression of these MMPs while increasing TIMP-1 expression, at both the mRNA and protein levels. In addition, IL-1β-induced activation of nuclear factor kappa B (NF-κB) and the degradation of inhibitor of κB (IκB)-α were suppressed by CGA. In rabbits, CGA decreased cartilage degradation as assessed by morphological and histological analyses. The down-regulation of MMP-1, MMP-3, and MMP-13 expression and up-regulation of TIMP-1 expression were also detected in CGA-treated cartilage compared with vehicle-treated cartilage, confirming these findings in an in vivo model. Taken together, these findings indicate that CGA may be considered as a possible candidate agent in the treatment of OA.
AuthorsWei-Ping Chen, Jing-Li Tang, Jia-Peng Bao, Peng-Fei Hu, Zhong-Li Shi, Li-Dong Wu
JournalInternational immunopharmacology (Int Immunopharmacol) Vol. 11 Issue 1 Pg. 23-8 (Jan 2011) ISSN: 1878-1705 [Electronic] Netherlands
PMID20951230 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier B.V. All rights reserved.
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-1beta
  • NF-kappa B
  • Recombinant Proteins
  • Chlorogenic Acid
  • Matrix Metalloproteinases
Topics
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, therapeutic use)
  • Cell Survival (drug effects)
  • Cells, Cultured
  • Chlorogenic Acid (administration & dosage, therapeutic use)
  • Chondrocytes (immunology)
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression (drug effects)
  • Interleukin-1beta (immunology)
  • Matrix Metalloproteinases (biosynthesis, genetics)
  • NF-kappa B (immunology)
  • Osteoarthritis (drug therapy, immunology)
  • Rabbits
  • Recombinant Proteins (immunology)
  • Reverse Transcriptase Polymerase Chain Reaction

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