Analysis of gp130-induced signals which regulate osteclast formation and function

点击翻译按钮获取中文摘要

Existence of soluble interleukin-6 receptors (sIL-6R) triggers osteoclast formation induced by IL-6, a gp130-mediated cytokine, in co-culture of mouse osteoblastic cells and spleen cells. However, interleukin-11 (IL-11) and oncostatin M,which also use gp130 as a common signal transducer, stimulated osteoclast formation in the absence of respective soluble type receptors. We have studied how gp130-mediated signals regulate osteoclast formation and function. (1) RT-PCR analysis revered that osteoblastic cells expressed receptors for IL-11 but not for IL-6. Using transgenic mouse expressing IL-6 receptors (IL-6R), it was shown that the expression of IL-6R in osteoblastic cells is indispensable for osteoclast formation induced by IL-6 in co-cultures of mouse spleen cells and osteoblastic cells. (2) We examined the possible involvement of IL-6 together with sIL-6R in joinjt disruption of rheumatoid arthritis (RA) patients. Osteoclast-like multinucleated cells were found in synovium of RA patients. Synovial fluids from RA patients contained significantly elevated concentrations of both IL-6 and sIL-6R in comparison with those from osteoarthritis patients. (3) When osteoclasts were placed on dentine slices, they formed resorption pits within 24hr. Cytokines such as IL-6, IL-11 and oncostatin M did not influence pit forming activity of osteoclasts. In addition, osteoclast function was not affected by adding anti-mouse gp130 antibody to the pit formation assay. (4) Bone-resorbing factors such as 1alpha, 25(OH)_2D_3, PTH and PGE_2 stimulated production of IL-11 by osteoblastic cells. Anti-mouse gp130 antibody inhibited osteoclast formation induced by these bone-resorbing factors in co-culture of mouse osteoblastic cells and spleen cells. These results suggest that signals mediated by gp130 are involved in osteoclast formation but not in osteoclast function.