Osteoclast differentiation factor mediates an essential signal for bone resorption induced by 1 alpha,25-dihydroxyvitamin D3, prostaglandin E2, or parathyroid hormone in the microenvironment of bone.
Osteoclast differentiation factor (ODF), a ligand for osteoprotegerin (OPG)/osteoclastogenesis-inhibitory factor (OCIF), induces osteoclast-like cell formation in vitro. To elucidate the role of ODF in the microenvironment of bone, we examined effects of ODF, OPG/OCIF, and anti-ODF polyclonal antibody on bone resorption using a fetal mouse long bone culture system. A genetically engineered soluble-form ODF (sODF) elicited bone resorption in a concentration-dependent manner and OPG/OCIF blocked the bone resorption. Anti-ODF polyclonal antibody, which neutralizes ODF activity, negated bone resorption induced by 1 alpha,25-dihydroxyvitamin D3, parathyroid hormone, or prostaglandin E2. OPG/OCIF also abolished bone-resorbing activity elicited by these bone-resorbing agents. Interleukin 1 alpha-stimulated bone resorption was also significantly suppressed by anti-ODF polyclonal antibody and OPG/OCIF. Thus, we conclude that ODF plays a critical role in bone resorption in the microenvironment of bone.
Tsukii
K
K
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd., Tochigi, Japan.
Shima
N
N
Mochizuki
S
S
Yamaguchi
K
K
Kinosaki
M
M
Yano
K
K
Shibata
O
O
Udagawa
N
N
Yasuda
H
H
Suda
T
T
Higashio
K
K
D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced* / Q000503:physiopathology* / Q000517:prevention & control; D002117:Calcitriol / Q000494:pharmacology*; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D046508:Culture Techniques; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology*; D006023:Glycoproteins / Q000502:physiology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D053244:Osteoprotegerin; D010281:Parathyroid Hormone / Q000494:pharmacology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology
D002352:Carrier Proteins; D016207:Cytokines; D006023:Glycoproteins; D008024:Ligands; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D002117:Calcitriol; D015232:Dinoprostone