Histology of a proximal interphalangeal joint, showing phases of the degenerative process in CIA. (Top left) A healthy, unaffected joint in a rhesus monkey with collagen-induced arthritis (CIA) shows intact cartilage and no marked activity of the subchondral bone. (Top right) Joint destruction starts where the synovium overgrows the cartilage. A hyperplastic synovium resulting in pannus formation produces factors such as cytokines and matrix metalloproteases mediating the destruction of the cartilage. (Bottom left) In the late phase of the disease, cartilage can be completely eroded and also the underlying bone can be seriously damaged.