title: Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin.
abstract: Osteoclasts are multinucleated cells that resorb bone. Osteoclastogenesis 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 osteoclastogenesis 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 strength of their bones dramatically decreased. These results demonstrate that OCIF/OPG is a key factor acting as a negative regulator against osteoclastogenesis. The OCIF/OPG knockout mice provide the first animal model for osteoporosis without other obvious abnormalities.
authors.affiliation: Research Institute of Life Science, Snow Brand Milk Products, Co., Ltd., Tochigi, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Mizuno
authors.forename: N
authors.initials: N
authors.lastname: Amizuka
authors.forename: K
authors.initials: K
authors.lastname: Irie
authors.forename: A
authors.initials: A
authors.lastname: Murakami
authors.forename: N
authors.initials: N
authors.lastname: Fujise
authors.forename: T
authors.initials: T
authors.lastname: Kanno
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: N
authors.initials: N
authors.lastname: Nakagawa
authors.forename: H
authors.initials: H
authors.lastname: Yasuda
authors.forename: S
authors.initials: S
authors.lastname: Mochizuki
authors.forename: T
authors.initials: T
authors.lastname: Gomibuchi
authors.forename: K
authors.initials: K
authors.lastname: Yano
authors.forename: N
authors.initials: N
authors.lastname: Shima
authors.forename: N
authors.initials: N
authors.lastname: Washida
authors.forename: E
authors.initials: E
authors.lastname: Tsuda
authors.forename: T
authors.initials: T
authors.lastname: Morinaga
authors.forename: K
authors.initials: K
authors.lastname: Higashio
authors.forename: H
authors.initials: H
authors.lastname: Ozawa
mesh_terms: D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology; D018390:Gene Targeting / Q000379:methods; D006023:Glycoproteins / Q000172:deficiency*; D006651:Histocytochemistry; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D010024:Osteoporosis / Q000503:physiopathology*; D053244:Osteoprotegerin; D010641:Phenotype; D011859:Radiography; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor
chemical_list: D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506031:Tnfrsf11b protein, mouse