Abstract
We investigated the bone phenotype of mice with generalized lymphoproliferative disorder (gld) due to a defect in the Fas ligand-mediated apoptotic pathway. C57BL/6-gld mice had greater whole body bone mineral density and greater trabecular bone volume than their wild-type controls. gld mice lost 5-fold less trabecular bone and had less osteoclasts on bone surfaces after ovariectomy-induced bone resorption. They also formed more bone in a model of osteogenic regeneration after bone marrow ablation, had less osteoclasts on bone surfaces and less apoptotic osteoblasts. gld and wild-type mice had similar numbers of osteoclasts in bone marrow cultures, but marrow stromal fibroblasts from gld mice formed more alkaline phosphatase-positive colonies. Bone diaphyseal shafts and bone marrow stromal fibroblasts produced more osteoprotegerin mRNA and protein than wild-type mice. These findings provide evidence that the disturbance of the bone system is a part of generalized lymphoproliferative syndrome and indicates the possible role of osteoprotegerin as a regulatory link between the bone and immune system.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / genetics
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Apoptosis / immunology
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Bone Density / genetics*
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Bone Density / immunology*
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Bone Marrow Cells / metabolism
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Bone Resorption / genetics
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Bone Resorption / immunology
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Bone Resorption / pathology
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Bone and Bones / metabolism
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Cells, Cultured
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Fas Ligand Protein
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Female
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Glycoproteins / biosynthesis
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Glycoproteins / genetics
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Ligands
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Lymphoproliferative Disorders / genetics*
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Lymphoproliferative Disorders / immunology
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Lymphoproliferative Disorders / metabolism
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Lymphoproliferative Disorders / physiopathology*
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Osteoclasts / pathology
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Osteoprotegerin
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Phenotype
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RNA, Messenger / biosynthesis
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Receptors, Cytoplasmic and Nuclear / biosynthesis
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Tumor Necrosis Factor
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Stromal Cells / metabolism
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fas Receptor / physiology
Substances
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Fas Ligand Protein
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Fasl protein, mouse
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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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RNA, Messenger
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Receptors, Cytoplasmic and Nuclear
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Receptors, Tumor Necrosis Factor
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Tnfrsf11b protein, mouse
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fas Receptor