Development of in vitro model of bone destruction by cultured rheumatoid synovium and its inhibition

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Osteoclasts, bone resorbing cells in human tissues, may be involved in the process of rheumatoid bone destruction. To test this hypothesis, we developed an in vitro model of bone destruction by osteoclast-like cells derived from cultured rheumatoid synovial tissue without using any inducers. When a piece of rheumatoid synovial tissue was cultured on the plate, fibroblast- and macrophage-like cells came out from the tissue and proliferated in the coexistence of lymphocytes. After 14 days of culture, multinucleated cells with tartrate-resistant acid phosphatase activity appeared. These cells expressed vacuolar HィイD1+ィエD1-ATPase, the vitronectin receptor, and cathepsin K. Although [ィイD1125|ィエD1]-salmon calcitonin binding was very low, the cells contained ringed structures of F-actin and showed strong bone resorbing activity on ivory slices. Proliferation of macrophage-like cells and formation of multinucleated cells continued during 6 months of culture in the presence of fibroblast-like cells. The bone-resorbing activity of multinucleated cells derived from rheumatoid synovial tissue was much higher than that of cells from osteoarthritis synovial tissue, and was related to the disease activity of rheumatoid arthritis. Our culture system reproduced in vitro the process of bone destruction by rheumatoid synovium, including the proliferation and fusion of precursor cells, polarization, activation, and bone tissue resorption. This system may provide a tool for understanding the mechanisms of bone destruction in rheumatoid arthritis and for the development of new therapies to prevent bone destruction.