Increased bone mass is a part of the generalized lymphoproliferative disorder phenotype in the mouse.
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.
Katavić
Vedran
V
Croatian Institute for Brain Research and Department of Anatomy, Zagreb University School of Medicine, Zagreb, Croatia.
Lukić
Ivan Kresimir
IK
Kovacić
Natasa
N
Grcević
Danka
D
Lorenzo
Joseph A
JA
Marusić
Ana
A
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D015519:Bone Density / Q000235:genetics* / Q000276:immunology*; D001854:Bone Marrow Cells / Q000378:metabolism; D001862:Bone Resorption / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D008024:Ligands; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010010:Osteoclasts / Q000473:pathology; D053244:Osteoprotegerin; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor; D017154:Stromal Cells / Q000378:metabolism; D019014:fas Receptor / Q000502:physiology
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006023:Glycoproteins; D008024:Ligands; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506031:Tnfrsf11b protein, mouse; D019014:fas Receptor