VEGFR-1 TK signaling is involved in arthritis by modulating hematopoiesis and promoting the differentiation of monocytes/macrophages. A schematic model of the VEGFR-1 TK signals associated with arthritis. (Top) Immature monocytes/macrophages derived from BM hematopoietic cells differentiate and migrate into the circulation. VEGFR-1 is expressed in monocyte/macrophage lineages. VEGFR-1 signals mobilize inflammatory cells to the peripheral tissues and RA joints and stimulate secretion of inflammatory cytokines to promote RA. (Bottom) VEGFR-1 signal–deficient macrophages show suppressed cytokine secretion, phagocytosis, and VEGF-dependent migration, resulting in a decrease in RA.