| Theme |
Osteoimmunology |
| Title |
Regulation of osteoclast development by immunoglobulin-like receptors |
| Author |
Toshiyuki Takai |
Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University |
| Author |
Masanori Inui |
Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University |
| Author |
Yu Mori |
Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University |
| [ Summary ] |
DAP12 and FcRγ are typical immunoreceptor signal activator proteins that associate with multiple immunoglobulin-like receptors (IgLR) on various immune cells. DAP12 deficient (DAP12-l-) mice develop mild osteopetrosis in vivo, whereas the in vitro osteoclast induction from DAP12-l- bone marrow cells yields immature cells with greatly attenuated bone resorption activity. Mice deficient in FcRγ did not display any remarkable degree of osteopetrosis. However, those animals doubly deficient in DAP12 and FcRγ exhibit much more severe osteopetrosis than DAP12-l- mice, suggesting that either DAP12 or FcRγ is required for normal bone remodeling in vivo. Thus, activation signals initiated by multiple IgLR associating with DAP12 and FcRγ are indispensable for the development of osteoclasts in concert with RANKL and M-CSF. |