Alleviation of Osteoarthritis by Trichostatin A, a Histone Deacetylase Inhibitor, in Experimental Osteoarthritis

Mol Biol Rep. 2010 Dec;37(8):3967-72. doi: 10.1007/s11033-010-0055-9. Epub 2010 Mar 17.

Abstract

This study investigated the effects of the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) on cartilage degradation in an experimental model of osteoarthritis (OA). Thirty-two male New Zealand rabbits underwent unilateral anterior cruciate ligament transection (ACLT) on left knee joints to induce OA and were randomly divided into two groups (n = 16), the TSA group was injected intra-articularly with 0.3 ml TSA [250 ng/ml in the dimethylsulphoxide (DMSO)], the OA group received DSMO since 4 weeks after operation once a week for 5 weeks. Rabbits were killed seven days after the last injection. Left knee cartilage was harvested for morphological, histological and genetic analysis. Another ten rabbits were used for normal control and received no injection. The TSA group showed less cartilage degradation as compared to the OA group assessed by morphological and histological evaluation. Gene expression of matrix metalloproteinase-1 (MMP-1), MMP-3, MMP-13, and interleukin-1 (IL-1) was increased significantly in the OA group compared to the normal group. The elevated expression was reduced by TSA. Our results suggest that TSA could be considered as a potential agent for treatment for OA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / enzymology
  • Cartilage, Articular / pathology
  • Femur / drug effects
  • Femur / pathology
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Hydroxamic Acids / pharmacology
  • Hydroxamic Acids / therapeutic use*
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism
  • Male
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / enzymology
  • Osteoarthritis / pathology
  • Rabbits

Substances

  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Interleukin-1
  • trichostatin A
  • Matrix Metalloproteinases