Differentiation of monocytes into multinucleated giant bone-resorbing cells: two-step differentiation induced by nurse-like cells and cytokines

Bone resorption in the joints is the characteristic finding in patients wit h rheumatoid arthritis (RA). Osteoclast-like cells are present in the synov ial tissues and invade the bone of patients with RA. The characteristics of these cells are not completely known. In the work reported here, we genera ted these cells from peripheral-blood monocytes from healthy individuals. T he monocytes were co-cultured with nurse-like cells from synovial tissues o f patients with RA (RA-NLCs). Within 5 weeks of culture, the monocytes were activated and differentiated into mononuclear cells positive for CD14 and tartrate-resistant acid phosphatase (TRAP). These mononuclear cells then di fferentiated into multinucleated giant bone-resorbing cells after stimulati on with IL-3, IL-5, IL-7, and/or granulocyte-macrophage-colony-stimulating factor. TRAP-positive cells with similar characteristics were found in syno vial fluid from patients with RA. These results indicate that multinucleate d giant bone-resorbing cells are generated from monocytes in two steps: fir st, RA-NLCs induce monocytes to differentiate into TRAP-positive mononuclea r cells, which are then induced by cytokines to differentiate into multinuc leated giant bone-resorbing cells.