SEVERE OSTEOPOROSIS IN MICE LACKING OSTEOCLASTOGENESIS INHIBITORY FACTOR OSTEOPROTEGERIN

Osteoclasts are multinucleated cells that resorb bone. Osteoclastogene sis inhibitory factor (OCIF), also called osteoprotegerin (OPG), acts as a naturally occurring decoy receptor for osteoclast differentiation factor, which mediates an essential signal to osteoclast progenitors for their differentiation into osteoclasts. Here we show that the OCIF /OPG knockout mice exhibited severe osteoporosis due to enhanced osteo clastogenesis when they grew to be adults. These mice were viable and fertile. They exhibited marked bone loss accompanied by destruction of growth plate and lack of trabecular bone in their femurs. The strengt h of their bones dramatically decreased. These results demonstrate tha t OCIF/OPG; is a key factor acting as a negative regulator against ost eoclastogenesis. The OCIF/OPG knockout mice provide the first animal m odel for osteoporosis without other obvious abnormalities. (C) 1998 Ac ademic Press.