Based on these data, MIF appears to directly inhibit osteoclastogenesis in vitro but its effects on osteoclasts in vivo are complex and may result from decreased RANKL expression in the osteoclast precursor cells from MIF knockout mice that were exposed to low levels of RANKL in vivo and as a result these cells have increased sensitivity to RANKL in vitro when cultured at high density.The MIF knockout mice that they used, had a marked resistance to lipopolysaccharide-induced endotoxic shock, and decreased TNFα production in response to lipopolysaccharide treatment. Here, TNF is linked to Shock.