HUMAN OSTEOCLAST FORMATION AND BONE-RESORPTION BY MONOCYTES AND SYNOVIAL MACROPHAGES IN RHEUMATOID-ARTHRITIS

Objective-To determine whether synovial macrophages and monocytes isol ated fi om patients with rheumatoid arthritis patients are capable of differentiating into osteoclastic bone resorbing cells; and the cellul ar and humoral conditions required for this to occur. Methods-Macropha ges isolated from the synovium and monocytes from the peripheral blood of rheumatoid arthritis patients were cultured on bone slices and cov erslips, in the presence and absence of UMR 106 rat osteoblast-like ce lls, 1,25-dihydroxy vitamin D-3 (1,25(OH)(2)D-3) and macrophage colony stimulating factor (M-CSF), and assessed for cytochemical and functio nal evidence of osteoclast differentiation. Results-Isolated calcitoni n receptor (CTR), tartrate resistant acid phosphatase (TRAP), and vitr onectin receptor (VNR) negative, CD11b and CD14 positive monocytes and macrophages differentiated into CTR, TRAP, and VNR positive multinucl eated cells capable of extensive lacunar bone resorption when co-cultu red for 14 d with UMR 106 cells in the presence 1,25(OH)(2)D-3 and M-C SF. Conclusions-Mononuclear phagocytes (monocytes and macrophages) fro m rheumatoid arthritis patients are capable of differentiating into mu ltinucleated cells showing all the cytochemical and functional criteri a of mature osteoclasts. Synovial macrophage-osteoclast differentiatio n may represent an important cellular mechanism in the bone destructio n associated with rheumatoid arthritis.