Effect of TNF-alpha on murine osteoclast differentiation

The purpose of this study was to investigate the effect of TNF-alpha on osteoclast differentiation in primary murine bone marrow cell culture with and without RANKL.M-CSF-dependent bone marrow cells were isolated from 5-6 weeks old mice, and cultured in the presence of M-CSF (25 microg/L) with different concentrations of TNF-alpha (0, 1, 10, 100 microg/L) for 5 days, the formation of TRAP(+) multinucleated cells was observed. These cells were also cultured in the presence of both RANKL (30 microg/L) and M-CSF (25 microg/L) with or without 10 microg/L TNF-alpha for 4, 5, 6 and 9 days. The number of TRAP(+) multinucleated cells and resorption pits on dentine slices were counted under light microscope.In the absence of RANKL, TNF-alpha was unable to induce osteoclast formation from murine bone marrow precursors. In the presence of RANKL, TNF-alpha augmented osteoclastogenesis and bone resorption, and this effect occurred only on the early stage.TNF-alpha enhances RANKL-induced osteoclast formation and function, but cannot substitute for RANKL. TNF-alpha stimulates osteoclast differentiation, but not survival.PubMed04433-53