OBJECTIVE: To investigate the effect of the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), on joint inflammation and cartilage degeneration in a collagen antibody-induced arthritis (CAIA) mouse model. METHODS: CAIA mice were given daily subcutaneous injections of various concentrations of TSA (0, 0.5, 1.0, and 2.0 mg/kg) and 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 (MMP)-3, MMP-13, tissue inhibitor of MMP-1 (TIMP-1), and acetyl-H4 by chondrocytes, another group of mice was sacrificed on Day 6. In vitro direct effect of TSA was examined by real-time PCR for mRNA of type II collagen, aggrecan, MMP-3, and MMP-13 in murine chondrogenic ATDC5 cells after pro-inflammatory cytokine stimulation. 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 significantly lower in the TSA 2.0 mg/kg group compared to the other TSA-treated groups. On immunohistochemistry, the number of MMP-3 and MMP-13-positive chondrocytes was significantly lower in the TSA 2.0 mg/kg group than in the control group. In contrast, the number of TIMP-1-positive cells and acetyl-histone H4-positive cells was significantly higher in the TSA 2.0mg/kg group than in the control group. TSA suppressed interleukin 1-beta and tumor necrosis factor-alpha-stimulated up-regulation of MMP-3, but not MMP-13 mRNA expression by ATDC5. CONCLUSION: The systemic administration of TSA ameliorated synovial inflammation in CAIA mice. Subsequently cartilage destruction was also suppressed by TSA, at least in part, by modulating chondrocyte gene expression.
OBJECTIVE: To investigate the effect of the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), on joint inflammation and cartilage degeneration in a collagen antibody-induced arthritis (CAIA) mouse model. METHODS: CAIA mice were given daily subcutaneous injections of various concentrations of TSA (0, 0.5, 1.0, and 2.0 mg/kg) and 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 (MMP)-3, MMP-13, tissue inhibitor of MMP-1 (TIMP-1), and acetyl-H4 by chondrocytes, another group of mice was sacrificed on Day 6. In vitro direct effect of TSA was examined by real-time PCR for mRNA of type II collagen, aggrecan, MMP-3, and MMP-13 in murine chondrogenic ATDC5 cells after pro-inflammatory cytokine stimulation. 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 significantly lower in the TSA 2.0 mg/kg group compared to the other TSA-treated groups. On immunohistochemistry, the number of MMP-3 and MMP-13-positive chondrocytes was significantly lower in the TSA 2.0 mg/kg group than in the control group. In contrast, the number of TIMP-1-positive cells and acetyl-histone H4-positive cells was significantly higher in the TSA 2.0mg/kg group than in the control group. TSA suppressed interleukin 1-beta and tumor necrosis factor-alpha-stimulated up-regulation of MMP-3, but not MMP-13 mRNA expression by ATDC5. CONCLUSION: The systemic administration of TSA ameliorated synovial inflammation in CAIA mice. Subsequently cartilage destruction was also suppressed by TSA, at least in part, by modulating chondrocyte gene expression.
Authors: Elizabeth W Bradley; Lomeli R Carpio; Andre J van Wijnen; Meghan E McGee-Lawrence; Jennifer J Westendorf Journal: Physiol Rev Date: 2015-10 Impact factor: 37.312
Authors: Rogier A Quax; Laura Manenschijn; Jan W Koper; Johanna M Hazes; Steven W J Lamberts; Elisabeth F C van Rossum; Richard A Feelders Journal: Nat Rev Endocrinol Date: 2013-10-01 Impact factor: 43.330
Authors: Nicole L Regna; Cristen B Chafin; Sarah E Hammond; Abdul G Puthiyaveetil; David L Caudell; Christopher M Reilly Journal: Clin Immunol Date: 2014-01-15 Impact factor: 3.969