A NEW MECHANISM OF BONE DESTRUCTION IN RHEUMATOID-ARTHRITIS - SYNOVIAL FIBROBLASTS INDUCE OSTEOCLASTOGENESIS

Bone-resorbing multinucleated cells were efficiently formed in primary culture of cells isolated from synovial tissues of patients with rheu matoid arthritis in 2-3 weeks in the presence of 1,25(OH)(2)vitaminD(3 ) without any additional stromal cells, and that formation was further facilitated by macrophage-colony stimulating factor. Furthermore, we show that osteoclast-like cells are formed in co culture of peripheral blood mononuclear cells and rheumatoid synovial fibroblasts obtained by continued sub-cultures. The multinucleated cells showed all the phe notypical and functional characteristics of osteoclasts including the expression of tartrate resistant acid phosphatase, vitronectin recepto rs, receptors for human calcitonin and the ability to resorb bone. The se results indicate that synovial macrophages are capable of different iating into osteoclasts in the presence of rheumatoid synovial fibrobl asts which can support differentiation of monocytes/ macrophages, impl icating that osteoclasts generated within the synovial membrane are pr obably involved in bone destruction in rheumatoid arthritis. (C) 1997 Academic Press.