Nasu Y et al. - The systemic administration of trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, ameliorated synovial inflammation and subsequently cartilage destruction in collagen antibody-induced arthritis (CAIA) mice. Methods
To study the effect of TSA, on joint inflammation and cartilage degeneration
CAIA mice were given daily sc injections of various concentrations of TSA (0, 0.5, 1.0, and 2.0 mg/kg)
Various parameters were monitored for 14 days
On Day 15, the hind paws were examined histologically
To investigate the effects of TSA on the expressions of matrix metalloproteinase and acetyl-H4 by chondrocytes, another group of mice was sacrificed on d6
In vitro direct effect of TSA was examined by RT-PCR for mRNA of type II collagen, aggrecan, MMP-3, and MMP-13
Results
In the TSA-treated group, clinical arthritis was significantly ameliorated in a dose-dependent manner
The severity of synovial inflammation and the cartilage destruction score were lower in the TSA 2.0 mg/kg group vs other TSA-treated groups
On IHC, the number of MMP-3 and MMP-13-positive chondrocytes was lower in the TSA 2.0 mg/kg group vs control group
The no of TIMP-1-positive cells and acetyl-histone H4-positive cells was higher in the TSA 2.0 mg/kg group vs control group
TSA suppressed IL1-β and TNF-α-stimulated up-regulation of MMP-3, but not MMP-13 mRNA expression by ATDC5
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