The effect of geranylgeranylacetone on human osteoclastogenesis and synovitis in patients with rheumatoid arthritis

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Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with synovitis and bone destruction. The levels of monocyte/macrophage-derived cytokines, including TNFα, interleukin-1 (IL-1), and IL-6, and the T cell-derived cytokine, IL-17, all of which are involved in the pathogenesis of RA, are elevated in the synovial fluid of RA patients.<BR>Geranylgeranylacetone (GGA), an acyclic polyisoprenoid known as teprenone, has been widely used as an antiulcer drug. We have reported that GGA inhibits human osteoclastgenesis, and that GGA increases the bone mineral density in ovariectomized rats and tail-suspended rats. These effects are due to inhibiting the prenylation of geranylgeranylpyrophosphate (GGPP) by GGA in the mevalonate pathway. Recently, we also demonstrated that GGA induces cell death in fibroblast-like synoviocytes from patients with RA. These findings suggest that GGA may be available as a new agent for RA and osteoporosis.
日本炎症・再生医学会の論文