However, several points of evidence contradict such a mechanism: proinflammatory mediators, such as TNF, are negative regulators and not positive regulators of osteoblasts; osteoclasts but not osteoblasts dominate the areas close to synovial inflammatory tissue; accumulation of osteoblasts is always linked to the presence of osteoclasts and is not seen as an isolated process upon emergence of arthritis; and selective blockade of bone resorption by RANKL blockade does not interfere with synovitis, but does block the anabolic response. This evidence concerns the gene TNFSF11 and Arthritis.