TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis

There is considerable evidence that osteoclasts are involved in the pathoge nesis of focal bone erosion in rheumatoid arthritis. Tumor necrosis factor- related activation-induced cytokine, also known as receptor activator of nu clear factor-kappa beta ligand (TRANCE/ RANKL) is an essential factor for o steoclast differentiation. In addition to its role in osteoclast differenti ation and activation, TRANCE/RANKL also functions to augment T-cell dendrit ic cell cooperative interactions. To further evaluate the role of osteoclas ts in focal bone erosion in arthritis, we generated inflammatory arthritis in the TRANCE/RANKL knockout mouse using a serum transfer model that bypass es the requirement for T-cell activation. These animals exhibit an osteopet rotic phenotype characterized by the absence of osteoclasts. Inflammation, measured by clinical signs of arthritis and histopathological scoring, was comparable in wild-type and TRANCE/ RANKL knockout mice. Microcomputed tomo graphy and histopathological analysis demonstrated that the degree of bone erosion in TRANCE/RANKL knockout mice was dramatically reduced compared to that seen in control littermate mice. in contrast, cartilage erosion was pr esent in both control littermate and TRANCE/RANKL knockout mice. These resu lts confirm the central role of osteoclasts in the pathogenesis of bone ero sion in arthritis and demonstrate distinct mechanisms of cartilage destruct ion and bone erosion in this animal model of arthritis.