Abstract
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.
MeSH terms
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Animals
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Bone Resorption / chemically induced*
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Bone Resorption / physiopathology*
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Bone Resorption / prevention & control
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Calcitriol / pharmacology*
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Carrier Proteins*
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Cell Differentiation / drug effects
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Cell Differentiation / physiology
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Culture Techniques
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Cytokines / pharmacology
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Cytokines / physiology
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Dinoprostone / pharmacology*
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Glycoproteins / physiology
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Ligands
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Membrane Glycoproteins / pharmacology
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Membrane Glycoproteins / physiology*
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Mice
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Osteoclasts / cytology
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Osteoclasts / drug effects
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Osteoclasts / physiology*
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Osteoprotegerin
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Parathyroid Hormone / pharmacology*
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RANK Ligand
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Receptor Activator of Nuclear Factor-kappa B
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Receptors, Cytoplasmic and Nuclear*
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Receptors, Tumor Necrosis Factor / physiology
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Recombinant Proteins / pharmacology
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Signal Transduction
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Tumor Necrosis Factor-alpha / pharmacology
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Tumor Necrosis Factor-alpha / physiology
Substances
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Carrier Proteins
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Cytokines
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Glycoproteins
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Ligands
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Membrane Glycoproteins
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Osteoprotegerin
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Parathyroid Hormone
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RANK Ligand
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Receptor Activator of Nuclear Factor-kappa B
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Receptors, Cytoplasmic and Nuclear
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Receptors, Tumor Necrosis Factor
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Recombinant Proteins
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Tnfrsf11a protein, mouse
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Tnfrsf11b protein, mouse
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Tnfsf11 protein, mouse
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Tumor Necrosis Factor-alpha
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Calcitriol
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Dinoprostone