title: Macrophage colony-stimulating factor and interleukin-6 release by periprosthetic cells stimulates osteoclast formation and bone resorption.
abstract: Periprosthetic bone loss is an important contributory factor for aseptic loosening of total joint replacements. It has recently been shown that osteoclast precursor cells are present in the wear particle-associated macrophage infiltrate found in the membrane surrounding loose implants and that these cells are capable of differentiating into osteoclastic bone-resorbing cells. Long-term co-culture of arthroplasty-derived macrophages and the rat osteoblast-like cell line, UMR-106, in the presence of 1,25(OH)2D3 results in the formation of numerous multinucleated cells that are positive for tartrate-resistant acid phosphatase and vitronectin receptor and capable of extensive lacunar bone resorption. The aim of this study was to determine the effect of cytokines/growth factors, known to be present in the arthroplasty membrane, on this process of osteoclast differentiation. During osteoclast formation, increased levels of macrophage colony-stimulating factor, interleukin-6, and to a lesser extent, interleukin-1beta, but not tumour necrosis factor alpha, were detected in the co-culture supernatants. Addition of neutralising antibodies to human interleukin-1beta or tumour necrosis factor alpha to the co-culture system did not inhibit osteoclast formation. In contrast, co-cultures to which neutralising antibodies to human macrophage colony-stimulating factor or interleukin-6 were added contained fewer cells positive for tartrate-resistant acid phosphatase and vitronectin receptor and formed significantly fewer resorption pits. Time-course studies showed that macrophage colony-stimulating factor and interleukin-6 increase osteoclast formation mainly in the early stages of osteoclast differentiation. These results indicate that the release of macrophage colony-stimulating factor and interleukin-6 by activated cells in the arthroplasty membrane is likely to contribute to pathological bone resorption associated with aseptic loosening by stimulating differentiation of mononuclear phagocyte osteoclast precursors into mature bone-resorbing cells.
authors.affiliation: Nuffield Department of Orthopaedic Surgery, University of Oxford, Headington, England.
authors.forename: S D
authors.initials: SD
authors.lastname: Neale
authors.forename: A
authors.initials: A
authors.lastname: Sabokbar
authors.forename: D W
authors.initials: DW
authors.lastname: Howie
authors.forename: D W
authors.initials: DW
authors.lastname: Murray
authors.forename: N A
authors.initials: NA
authors.lastname: Athanasou
mesh_terms: D000077:Acetabulum / Q000166:cytology / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000494:pharmacology; D019644:Arthroplasty, Replacement, Hip; D001862:Bone Resorption / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D005269:Femur / Q000166:cytology / Q000601:surgery; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism*; D016177:Macrophage-1 Antigen / Q000032:analysis; D008264:Macrophages / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000166:cytology* / Q000276:immunology; D010521:Periosteum / Q000166:cytology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D007375:Interleukin-1; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D016177:Macrophage-1 Antigen; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor