title: Pseudosynovial fluid from loosened total hip prosthesis induces osteoclast formation.
abstract: Interface tissue between the bone and loosening total hip implant is acidic and highly osteolytic. It is characterized by the formation of cathepsin K positive foreign body giant cells. Similar structures to those found in the normal joint surround the artificial hip joint. Cells in synovial membrane of the artificial hip generate synovial fluid that is called pseudosynovial fluid. Interface tissue fibroblasts are able to produce receptor activator of NF-kappaB ligand (RANKL), which can induce osteoclastogenesis during the loosening process. Western blot analysis indicated that RANKL is present in the pseudosynovial fluid. Pseudosynovial fluid induced cultured peripheral blood mononuclear cells to form multinuclear TRAP positive giant cells. In the presence of osteoprotegerin, the soluble RANKL decoy receptor, the number of TRAP positive multinuclear cells was reduced to half (p < 0.05). The multinuclear cells induced with pseudosynovial fluid contained active cathepsin K protein and were capable of bone matrix resorption in vitro. The cells were shown to express osteoclast phenotype markers, such as mRNA for cathepsin K, TRAP, and calcitonin receptor. It is therefore apparent that pseudosynovial fluid from patients with aseptic loosening of total hip prosthesis contains a potent osteoclastogenic factor RANKL that further suggests a favorable environment for osteoclast formation in the peri-implant tissues. It is thus concluded that suppression of RANKL activity may be beneficial in terms of increasing the lifetime of total hip prostheses.
authors.affiliation: Institute of Biomedicine/Anatomy, Biomedicum Helsinki, University of Helsinki, Finland.
authors.forename: Jami
authors.initials: J
authors.lastname: Mandelin
authors.forename: Mikko
authors.initials: M
authors.lastname: Liljeström
authors.forename: Tian-Fang
authors.initials: TF
authors.lastname: Li
authors.forename: Mari
authors.initials: M
authors.lastname: Ainola
authors.forename: Mika
authors.initials: M
authors.lastname: Hukkanen
authors.forename: Jari
authors.initials: J
authors.lastname: Salo
authors.forename: Seppo
authors.initials: S
authors.lastname: Santavirta
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000704:Analysis of Variance; D019644:Arthroplasty, Replacement, Hip; D015153:Blotting, Western; D001862:Bone Resorption; D002352:Carrier Proteins; D056657:Cathepsin K; D002403:Cathepsins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008562:Membrane Glycoproteins; D009000:Monocytes / Q000166:cytology*; D010010:Osteoclasts / Q000378:metabolism*; D053244:Osteoprotegerin; D010641:Phenotype; D011475:Prosthesis Failure; D053245:RANK Ligand; D012333:RNA, Messenger / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B; D018003:Receptors, Calcitonin / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013582:Synovial Fluid; D013583:Synovial Membrane / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018003:Receptors, Calcitonin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D016173:Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K