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Anti-rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen-induced arthritis in rodents

  1. H-S Lin1,2,†,
  2. C-Y Hu1,†,
  3. H-Y Chan1,
  4. Y-Y Liew1,
  5. H-P Huang1,
  6. L Lepescheux1,
  7. E Bastianelli1,
  8. R Baron1,3,
  9. G Rawadi1,
  10. P Clément-Lacroix1,*

Article first published online: 29 JAN 2009

DOI: 10.1038/sj.bjp.0707165

Issue

British Journal of Pharmacology

British Journal of Pharmacology

Volume 150, Issue 7, pages 862–872, April 2007

Additional Information

How to Cite

Lin, H.-S., Hu, C.-Y., Chan, H.-Y., Liew, Y.-Y., Huang, H.-P., Lepescheux, L., Bastianelli, E., Baron, R., Rawadi, G. and Clément-Lacroix, P. (2007), Anti-rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen-induced arthritis in rodents. British Journal of Pharmacology, 150: 862–872. doi: 10.1038/sj.bjp.0707165

Author Information

  1. 1

    Proskelia a Galapagos Company, Romainville, France

  2. 2

    Department of Pharmacy, National University of Singapore, Singapore, Singapore

  3. 3

    Department of Cell Biology and Orthopedics, Yale University School of Medicine, New Haven, CT, USA

  1. †

    These authors contributed equally to this work.

*ProStrakan, 102 Route de Noisy, Romainville 93230, France. E-mail: philippe.clement-lacroix@glpg.com

Publication History

  1. Issue published online: 29 JAN 2009
  2. Article first published online: 29 JAN 2009
  3. (Received April 24, 2006, Revised September 28, 2006, Accepted November 21, 2006)

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Keywords:

  • rheumatoid arthritis;
  • histone deacetylase inhibitor;
  • suberoylanilide hydroxamic acid;
  • MS-275

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.

British Journal of Pharmacology (2007) 150, 862–872. doi:10.1038/sj.bjp.0707165

View Full Article (HTML) Get PDF (341K)