Interaction of Human Recombinant Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand and Osteoprotegerin Could Contribute to Enhancement of the Erosive Processes Induced by Human Synovial Cells

Abstract

To the Editor: Rheumatoid arthritis (RA) is a chronic inflammatory disease for which the etiology is unknown. Patients with RA are known to have lower bone mineral density and are at risk of pathological fracture caused by cytokines produced by RA synovial fibroblasts, which have the potential to promote osteoclast formation and bone resorption. It is now clear that osteoclast formation and activation at the cartilage-pannus junction is an essential step in the destruction of bone matrix in RA1,2. Our aim was to investigate key factors that regulate focal bone erosion in RA, and their relationships with human recombinant tumor necrosis factor (TNF)-related apoptosis-inducing ligand (hr-TRAIL), in order to propose a strategy to block bone destruction in RA. A number of inflammatory cytokines found in the RA synovial tissue [interleukin 1 (IL-1), IL-1s, IL-6, TNF-α, and macrophage colony-stimulating factor] have the potential to promote osteoclast formation and bone resorption3,4. Cells within RA synovial fibroblasts also are substantial sources of soluble receptor activator of nuclear factor-κB (sRANKL) and osteoprotegerin … Address reprint requests to Dr. V. Nicolin; E-mail: nicolin{at}units.it