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Title: Anti-rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen-induced arthritis in rodents
Authors: Lin, H.-S. 
Hu, C.-Y.
Chan, H.-Y.
Liew, Y.-Y.
Huang, H.-P.
Lepescheux, L.
Bastianelli, E.
Baron, R.
Rawadi, G.
Clément-Lacroix, P.
Keywords: Histone deacetylase inhibitor
Rheumatoid arthritis
Suberoylanilide hydroxamic acid
Issue Date: Apr-2007
Citation: Lin, H.-S., Hu, C.-Y., Chan, H.-Y., Liew, Y.-Y., Huang, H.-P., Lepescheux, L., Bastianelli, E., Baron, R., Rawadi, G., Clément-Lacroix, P. (2007-04). Anti-rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen-induced arthritis in rodents. British Journal of Pharmacology 150 (7) : 862-872. ScholarBank@NUS Repository.
Abstract: Background and purpose: Rheumatoid arthritis (RA) is a chronic inflammatory disease. Histone deacetylase inhibitors (HDACi), a new class of anti-cancer agents, have recently been reported to exhibit potent anti-inflammatory activities. A proof of concept study was carried out with suberoylanilide hydroxamic acid (SAHA) and MS-275, two HDACi currently undergoing clinical investigations for various oncological indications. Experimental approach: The anti-rheumatic effects of SAHA and MS-275 were assessed in both mouse and rat collagen induced arthritis (CIA) models. Key results: SAHA exhibited moderate prophylactic efficacy. It attenuated paw swelling due to inflammation, decreased bone erosion in both mice and rats and reduced slightly the RA-induced bone resorption in rats. However, SAHA could not inhibit the onset of arthritis. In contrast, MS-275 displayed dramatic anti-rheumatic activities. In prophylactic intervention, high doses of MS-275 prevented bone erosion and markedly delayed the onset of arthritis; at low doses, MS-275 strongly attenuated paw swelling, bone erosion, and bone resorption associated with RA. Furthermore, the therapeutic efficacy of MS-275 was also documented. After the onset of arthritis, it could stop the disease progression and joint destruction.. An anti inflammatory effect of MS-275 was also confirmed through its capacity to decrease serum IL-6 and IL-1β levels in the CIA induced mouse model. The anti-rheumatic activity of MS-275 was also confirmed through histological observation. No synovial hyperplasia, pannus formation, cartilage or bone destruction were observed in the high dose prophylactic intervention in mice. Conclusion and implication: This study strongly supported HDACi as an innovative therapeutic strategy for RA. © 2007 Nature Publishing Group All rights reserved.
Source Title: British Journal of Pharmacology
ISSN: 00071188
DOI: 10.1038/sj.bjp.0707165
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