title: RANK (receptor activator of nuclear factor-kappaB) and RANKL expression in multiple myeloma.
abstract: The new members of the tumour necrosis factor (TNF) receptor-ligand family, receptor activator of nuclear factor-kappaB ligand (RANKL) and its receptor RANK, play a crucial role in osteoclast differentiation and activation. An increased expression of RANKL and/or RANK may be involved in the excessive bone resorption observed in multiple myeloma (MM). We used immunohistochemistry to study RANK and RANKL expression in bone marrow (BM) biopsies obtained at diagnosis in 15 MM patients, six patients with monoclonal gammopathy of undetermined significance (MGUS) and 10 normal BM biopsies. Plasma cells were not labelled with anti-RANKL or anti-RANK antibodies. In all biopsies, RANKL was expressed in endosteal bone surface, around vessels and in cells characterized by cytoplasmic expansions. These last cells did not express CD45 and were vimentin positive, corresponding to bone marrow stromal cells. Numerous stromal cells expressed RANKL in MM and MGUS specimens, with a greater expression in MM than in MGUS. Very few cells were stained with anti-RANKL in normal BM specimens. With the anti-RANK antibody, small mononuclear cells in the bone microenvironment were positive and were identified as erythroblast cells. In conclusion, we showed that RANKL was expressed in reticular stromal cells, with a greater intensity in myeloma specimens. These results suggest that RANKL overexpressed by bone marrow stromal cells may contribute to the high rate of bone resorption observed in MM.
authors.affiliation: Service de Rhumatologie, Hôpital de Bicêtre, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Roux
authors.forename: Véronique
authors.initials: V
authors.lastname: Meignin
authors.forename: Jeanine
authors.initials: J
authors.lastname: Quillard
authors.forename: Geri
authors.initials: G
authors.lastname: Meduri
authors.forename: Anne
authors.initials: A
authors.lastname: Guiochon-Mantel
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Fermand
authors.forename: Edwin
authors.initials: E
authors.lastname: Milgrom
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
mesh_terms: D001854:Bone Marrow Cells / Q000737:chemistry*; D002352:Carrier Proteins / Q000032:analysis*; D016022:Case-Control Studies; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000032:analysis*; D009101:Multiple Myeloma / Q000378:metabolism*; D053244:Osteoprotegerin; D010265:Paraproteinemias / Q000378:metabolism; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis*; D018124:Receptors, Tumor Necrosis Factor; D017154:Stromal Cells / Q000737:chemistry
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human