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Titolo:
Osteoprotegerin inhibits osteoclast formation and bone resorbing activity in giant cell tumors of bone
Autore:
Atkins, GJ; Bouralexis, S; Haynes, DR; Graves, SE; Geary, SM; Evdokiou, A; Zannettino, ACW; Hay, S; Findlay, DM;
Indirizzi:
Univ Adelaide, Dept Orthopaed & Trauma, Adelaide, SA, Australia Univ Adelaide Adelaide SA Australia ed & Trauma, Adelaide, SA, Australia Univ Adelaide, Dept Pathol, Adelaide, SA, Australia Univ Adelaide Adelaide SA Australia Dept Pathol, Adelaide, SA, Australia Flinders Med Ctr, Dept Orthopaed Surg, Daw Pk, SA, Australia Flinders Med Ctr Daw Pk SA Australia thopaed Surg, Daw Pk, SA, Australia Repatriat Gen Hosp, Daw Pk, SA, Australia Repatriat Gen Hosp Daw Pk SA Australia t Gen Hosp, Daw Pk, SA, Australia Inst Med & Vet Sci, Div Haematol, Adelaide, SA 5000, Australia Inst Med & Vet Sci Adelaide SA Australia 5000 delaide, SA 5000, Australia
Titolo Testata:
BONE
fascicolo: 4, volume: 28, anno: 2001,
pagine: 370 - 377
SICI:
8756-3282(200104)28:4<370:OIOFAB>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
HORMONE-RELATED PROTEIN; DIFFERENTIATION FACTOR; RECEPTOR ACTIVATOR; KAPPA-B; LIGAND; EXPRESSION; HYPERCALCEMIA; PATHOGENESIS; MALIGNANCY; RESORPTION;
Keywords:
giant cell tumor (GCT); osteoclast; osteoprotegerin (OPG); receptor activator nuclear factor of kappa B ligand; (RANKL); bone;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Findlay, DM Univ Adelaide, Royal Adelaide Hosp, Dept Orthopaed & Trauma, NTerrace, Adelaide, SA 5000, Australia Univ Adelaide N Terrace Adelaide SA Australia 5000 , Australia
Citazione:
G.J. Atkins et al., "Osteoprotegerin inhibits osteoclast formation and bone resorbing activity in giant cell tumors of bone", BONE, 28(4), 2001, pp. 370-377

Abstract

Osteolysis is a common complication of tumors that arise in, or metastasize to, bone. The recent discovery of key regulators of osteoclast formation and activity, including receptor activator of nuclear factor of KB Ligand (RANKL), RANK, and osteoprotegerin (OPG), may facilitate new treatment regimes for certain tumors associated with excessive bone loss. We recently showed that the stromal cells of osteolytic giant cell tumors (GCT) of bone express high levels of mRNA encoding RANKL, relative to mRNA for the RANKL antagonist, OPG, compared with the expression patterns of other lytic and nonlytic bone tumors. In this study, we found that expression of RANKL and OPG mRNA continued by the stromal element of these tumors in a constitutive manner for at least 9 days in the absence of giant cells, Immunostaining of unfractionated GCT cultured in vitro revealed punctate cytoplasmic/membranousstaining for RANKL and both cytoplasmic and extracellular matrix staining for OPG in stromal cells. Giant cells (osteoclasts) were negative for RANKLstaining, but stained brightly for cytoplasmic OPG protein, We also investigated the functional relevance of these molecules for GCT osteolysis by adding recombinant OPG and RANKL to cultured GCT cells. We found that OPG treatment potently and dose-dependently inhibited resorption of bone slices byGCT, and could also inhibit the formation of multinucleated osteoclasts from precursors within the GCT, These effects of OPG were reversed by stoichiometric concentrations of exogenous RANKL, These data indicate that both the processes of osteoclast formation and activation in GCT are promoted by RANKL. Therefore, GCT represent a paradigm for the direct stimulation of osteoclast formation and activity by tumor stromal cells, in contrast to the mechanisms described for osteolytic breast tumors and multiple myeloma, The demonstration of these relationships is important in developing approaches to limit tumor-induced osteolysis, (Bone 28:370-377; 2001) (C) 2001 by Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 14:29:36