期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 276, 期 3, 页码 868-872出版社
ACADEMIC PRESS INC
DOI: 10.1006/bbrc.2000.3577
关键词
osteoclast; TRANCE; RANKL; IFN-gamma; lineage switch
The immune system has profound effects on bone remodeling. IFN-gamma, a major product of immune cells, potently inhibits bone resorption, but its mechanism of action is unknown, We found in cultures of stroma-free mononuclear precursors that IFN-gamma strongly suppresses TRANCE/RANKL-induced osteoclast formation in a dose-dependent manner. This direct effect on osteoclast progenitors was not due to stimulation of NO production by IFN-gamma, as the NOS inhibitors 1400W and L-NAME were unable to reverse the suppression. However, TGF beta(1), which has opposing actions to IFN-gamma on diverse cellular functions, was able to antagonize the effect of IFN-gamma. This suggests that IFN-gamma prevents osteoclast formation by actively directing the differentiation of osteoclastic progenitors toward an alternative cytocidal lineage to the osteoclast. (C) 2000 Academic Press.
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