title: The osteoclastogenic molecules RANKL and RANK are associated with periprosthetic osteolysis.
abstract: Extensive osteolysis adjacent to implants is often associated with wear particles of prosthetic material. We have investigated if RANKL, also known as osteoprotegerin ligand, osteoclast differentiation factor or TRANCE, and its natural inhibitor, osteoprotegerin (OPG), may be important in controlling this bone loss. Cells isolated from periprosthetic tissues containing wear particles expressed mRNA encoding for the pro-osteoclastogenic molecules, RANKL, its receptor RANK, monocyte colony-stimulating factor (M-CSF), interleukin (IL)-1beta, tumour necrosis factor (TNF)alpha, IL-6, and soluble IL-6 receptor, as well as OPG. Osteoclasts formed from cells isolated from periprosthetic tissues in the presence and absence of human osteoblastic cells. When osteoclasts formed in the absence of osteoblastic cells, markedly higher levels of RANKL mRNA relative to OPG mRNA were expressed. Particles of prosthetic materials also stimulated human monocytes to express osteoclastogenic molecules in vitro. Our results suggest that ingestion of prosthetic wear particles by macrophages results in expression of osteoclast-differentiating molecules and the stimulation of macrophage differentiation into osteoclasts.
authors.affiliation: Department of Pathology, University of Adelaide, South Australia, Australia.
authors.forename: D R
authors.initials: DR
authors.lastname: Haynes
authors.forename: T N
authors.initials: TN
authors.lastname: Crotti
authors.forename: A E
authors.initials: AE
authors.lastname: Potter
authors.forename: M
authors.initials: M
authors.lastname: Loric
authors.forename: G J
authors.initials: GJ
authors.lastname: Atkins
authors.forename: D W
authors.initials: DW
authors.lastname: Howie
authors.forename: D M
authors.initials: DM
authors.lastname: Findlay
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism*; D010014:Osteolysis / Q000378:metabolism*; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D006023:Glycoproteins; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; 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; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor