title: Imbalance of RANKL/RANK/OPG system in interface tissue in loosening of total hip replacement.
abstract: In the differentiation of osteoclasts the differentiation factor (RANKL) interacts with the receptor activator of NF-kappaB (RANK) in a direct cell-to-cell contact between osteoblast and (pre)osteoclast. This is inhibited by soluble osteoprotegerin (OPG). The mRNA levels of both RANKL (p < 0.01) and RANK (p < 0.05) were high in peri-implant tissue and RANKL+ and RANK+ cells were found in such tissue. Double labelling also disclosed soluble RANKL bound to RANK+ cells. We were unable to stimulate fibroblasts to express RANKL in vitro, but monocyte activation with LPS gave a fivefold increase in RANK mRNA levels. In contrast to RANKL and RANK expression in peri-implant tissue, expression of OPG was restricted to vascular endothelium. Endothelial cell OPG mRNA levels were regulated by TNF-alpha and VEGF, but not by hypoxia. It is concluded that activated cells in the interface tissue overproduce both RANKL and RANK and they can interact without interference by OPG.
authors.affiliation: Institute of Biomedicine/Anatomy, Biomedicum Helsinki, University of Helsinki, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Mandelin
authors.forename: T F
authors.initials: TF
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Liljeström
authors.forename: M E
authors.initials: ME
authors.lastname: Kroon
authors.forename: R
authors.initials: R
authors.lastname: Hanemaaijer
authors.forename: S
authors.initials: S
authors.lastname: Santavirta
authors.forename: Y T
authors.initials: YT
authors.lastname: Konttinen
mesh_terms: D019644:Arthroplasty, Replacement, Hip; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008070:Lipopolysaccharides / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D053244:Osteoprotegerin; D011475:Prosthesis Failure; D053245:RANK Ligand; D012333:RNA, Messenger / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D008070:Lipopolysaccharides; 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