The role of "nurse-like cells" in bone resorbtion observed in patients with RA

Abstract

Synovial stromal fibroblastic cells were histologically suggested to be derived from the mesenchymal fibroblastic cells migrating from the ajacent bone marrow space. The membrane structures, cytokine productions, and other bioligical charactceristics are very similar among those fibroblastic cells derived from these two origins. These cells were found to have a characteristic biological function; holding lymphocytes underneath and supporting the development and proliferation of these cells. This function named was originalily found by Dr Wekerle (1980) in thymus cells of rats and mice, and those fibroblastic cells were named as nurse cells. We established the mesenchymal fibroblastic cell lines from synovial tissue and bone marrow cells in RA patients, and found the pseudoemperipolesis in these fibroblastic cells (nurse-like cells; NLC) just like nurse cells . We isolated monocytes from the peripheral blood of healthy donors, and incubated with NLC from RA patients (RA-NLC) . After 4 weeks of culture, TRAP- positive mononuclear cells with larger cytoplsma appeared. Monocytes cultured in medium alone died within 6 weeks. These TRAP- positive mononuclear cells differentiated into the multi-nucleated giant cells by incubating with some cytokines even in the absence of RA-NLC. These multinucleated giant cells showed the bone-resorbing activity by culturing on dentine slices. Considering that the significantly higher number of TRAP- positive mononuclear cells and the much more nucleated giant cells with higher bone-resorbing activity could be obtained from the iliac bone marrow of patients with more erosive disease group, RA-NLC could be considered to play important roles in highly activated bone destruction (including severe secondary osteoporosis) of RA patients.