Effects of diacerein at the molecular level in the osteoarthritis disease process

Abstract

In osteoarthritis (OA), the alterations in joint tissues are numerous and involve morphological, biochemical and metabolic changes and an upregulation of the inflammatory pathways. The focus of this article is a brief narrative review of the effects of diacerein, an antirheumatic drug from the anthraquinone chemical class, and its active metabolite, rhein, on the factors that participate in the complex interaction between OA tissues and cells leading to the progression of joint structural changes.

Keywords: cartilage; diacerein; osteoarthritis; rhein; subchondral bone; synovial membrane.

Figure 1.

Effect of diacerein/rhein on the IL-1 system. Diacerein/rhein reduces the level of IL-1 receptors leading to fewer receptors to form heterodimer complexes. Following the association of IL-1 with its specific cell surface receptor complex, there is an activation of downstream signalling pathways involving some MAP kinases. In OA articular tissues, rhein has been shown to reduce numerous genes including cytokines, nitric oxide (NO), metalloproteases (MMPs), a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS), etc., through the inhibition of the MEK/ERK intracellular cascade. IL-1B is produced as a precursor which is cleaved at the cell membrane by the IL-1 converting enzyme (ICE) which releases IL-1B as an active cytokine into the extracellular matrix. Rhein reduces the production of ICE leading to a reduction in IL-1B activation. The grey color indicates that lesser amounts of the factors are produced. The figure is from and reproduced with permission of TRB Chemedica International. MEK = mitogen-activated protein kinase (MAP kinase), ERK = extracellular-signal-regulated kinase.