title: Production of platelet-derived growth factor in aseptic loosening of total hip replacement.
abstract: Aseptic loosening is the predominant cause of total hip implant failure. It has been assumed that a layer or membrane, containing macrophages, fibroblasts and vascular endothelial cells, of synovial-like tissue develops at the implant-to-bone interface almost invariably and, with time, somehow leads to loosening of the components from the surrounding bone. These cells produce a variety of cytokines and proteolytic enzymes which stimulate bone resorption. Platelet derived growth factor (PDGF) may be one of the cytokines which stimulate bone resorption and contribute to aseptic loosening in total hip replacement (THR). Synovial-like membrane from the implant or cement-to-bone interface (n = 10) and pseudocapsule (n = 10) were obtained from ten patients operated on for aseptic loosening of THR. As a control, nine samples of connective tissues were obtained from patients who had mandibular or maxillary fractures fixed with bone implant. The avidin-biotin-peroxidase complex (ABC) method with polyclonal rabbit anti-human IgG against the A-chain and B-chain of PDGF was used for staining. ABC-alkaline phosphatase-anti-alkaline-phosphatase double staining with monoclonal mouse anti-human fibroblast IgG1 and CD68 antibodies was used to ascertain the cellular origin of PDGF. Results of the PDGF staining were quantitated by a semi-automatic VIDAS image analysis system. The PDGF-A and PDGF-B chain containing cells were found in all periprosthetic tissues, in particular in macrophages with phagocytosed particulate debris, but to some extent also in fibroblasts and in endothelial cells. The numbers of PDGF-A and PDGF-B chain positive cells per mm 2 in synovial-like interface membrane (1881 +/- 486 and 1877 +/- 214) and pseudocapsule (1786 +/- 236 and 1676 +/- 152) were higher (P < 0.01) around loose THR than in control tissue (821 +/- 112 and 467 +/- 150), respectively. The results of the present study suggest that PDGF is preferably expressed by macrophages, which to an increased extent produce it in the synovial-like interface membrane and pseudocapsular synovial-like membrane. Because of its role in bone resorption, it may well play a role in periprosthetic bone loss and aseptic loosening and deserves more detailed study as a mediator and potential target in the modulation or prevention of loosening of THR.
authors.affiliation: Department of Anatomy, University of Helsiniki, Finland.
authors.forename: J W
authors.initials: JW
authors.lastname: Xu
authors.forename: Y T
authors.initials: YT
authors.lastname: Konttinen
authors.forename: T F
authors.initials: TF
authors.lastname: Li
authors.forename: V
authors.initials: V
authors.lastname: Waris
authors.forename: J
authors.initials: J
authors.lastname: Lassus
authors.forename: M
authors.initials: M
authors.lastname: Matucci-Cerinic
authors.forename: T
authors.initials: T
authors.lastname: Sorsa
authors.forename: T S
authors.initials: TS
authors.lastname: Santavirta
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000497:Alloys; D019644:Arthroplasty, Replacement, Hip; D002452:Cell Count; D005260:Female; D005549:Foreign-Body Reaction / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017746:Joint Capsule / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008337:Mandibular Fractures / Q000378:metabolism / Q000601:surgery; D008440:Maxillary Fractures / Q000378:metabolism / Q000601:surgery; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011475:Prosthesis Failure; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
chemical_list: D000497:Alloys; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; C075278:platelet-derived growth factor A