Histone deacetylase inhibitors: new treatment options for inflammatory joint disease?

Abstract

Histone deacetylase inhibitors (HDIs) are a new class of compounds that are being developed for the treatment of malignancies such as cutaneous T-cell lymphoma. HDIs inhibit the removal of acetyl groups from histones. The histone acetylation process is dependent on two enzymes, histone acetyl transferase (HAT) and histone deacetylase (HDAC), and regulates the expression of genes, including those encoding cell survival or apoptosis. In addition to regulating cell growth, HDIs exert anti-inflammatory effects by controlling the production of anti-inflammatory cytokines; modulating the function of cells such as T cells, monocytes-macrophages, chondrocytes, and osteoclasts; and modulating angiogenesis. In several animal models of arthritis, HDIs improve the clinical manifestations and prevent damage to the bone and cartilage. In humans, the only relevant data available so far come from studies of HAT and HDAC expression in the synovial membrane of patients with rheumatoid arthritis. HDIs may hold promise for the treatment of inflammatory joint disease.

• Authors: Eric Toussirot, Kashif Aziz Khan, Ewa Bertolini, Daniel Wendling, Georges Herbein
• Journal: Joint bone spine (Joint Bone Spine) Vol. 77 Issue 5 Pg. 395-8 (Oct 2010) ISSN: 1778-7254 [Electronic] France
• PMID: 20729120 (Publication Type: Journal Article)
• Copyright: Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Chemical References

• Histone Deacetylase Inhibitors
• Histone Acetyltransferases

Topics

• Animals
• Arthritis, Rheumatoid (drug therapy, immunology)
• Histone Acetyltransferases (pharmacology, therapeutic use)
• Histone Deacetylase Inhibitors (pharmacology, therapeutic use)
• Humans
• Signal Transduction (physiology)
• Synovial Membrane (metabolism)