Fig. 4
Hypothesized model of the molecular and cellular mechanisms underlying arthritis. Straw-colored region in the top part indicates joint fluid. Boxes enclosed by broken lines indicate the lining, sublining, bone, and bone marrow. Tissue-resident-protective macrophages [76] become activated and differentiate and move into the lining space. CX3CR1low monocytes in the circulating blood produced in bone marrow migrate into the sublining space, where they become CXC3R1high macrophages and produce cytokines and chemokines [77]. Some activated macrophages, stimulated by M-CSF, differentiate into precursors with FoxM1 and are designated arthritis-associated osteoclastogenic macrophages (AtoM) [78]. Boxes indicate cytokines and chemokines, and solid lines show their action on cellular targets. Broken lines show the shift or differentiation of a cell. Double-headed arrows indicate cellular interaction