title: Effects on osteoclast and osteoblast activities in cultured mouse calvarial bones by synovial fluids from patients with a loose joint prosthesis and from osteoarthritis patients.
abstract: Aseptic loosening of a joint prosthesis is associated with remodelling of bone tissue in the vicinity of the prosthesis. In the present study, we investigated the effects of synovial fluid (SF) from patients with a loose prosthetic component and periprosthetic osteolysis on osteoclast and osteoblast activities in vitro and made comparisons with the effects of SF from patients with osteoarthritis (OA). Bone resorption was assessed by the release of calcium 45 (45Ca) from cultured calvariae. The mRNA expression in calvarial bones of molecules known to be involved in osteoclast and osteoblast differentiation was assessed using semi-quantitative reverse transcription-polymerase chain reaction (PCR) and real-time PCR. SFs from patients with a loose joint prosthesis and patients with OA, but not SFs from healthy subjects, significantly enhanced 45Ca release, effects associated with increased mRNA expression of calcitonin receptor and tartrate-resistant acid phosphatase. The mRNA expression of receptor activator of nuclear factor-kappa-B ligand (rankl) and osteoprotegerin (opg) was enhanced by SFs from both patient categories. The mRNA expressions of nfat2 (nuclear factor of activated T cells 2) and oscar (osteoclast-associated receptor) were enhanced only by SFs from patients with OA, whereas the mRNA expressions of dap12 (DNAX-activating protein 12) and fcrgamma (Fc receptor common gamma subunit) were not affected by either of the two SF types. Bone resorption induced by SFs was inhibited by addition of OPG. Antibodies neutralising interleukin (IL)-1alpha, IL-1beta, soluble IL-6 receptor, IL-17, or tumour necrosis factor-alpha, when added to individual SFs, only occasionally decreased the bone-resorbing activity. The mRNA expression of alkaline phosphatase and osteocalcin was increased by SFs from patients with OA, whereas only osteocalcin mRNA was increased by SFs from patients with a loose prosthesis. Our findings demonstrate the presence of a factor (or factors) stimulating both osteoclast and osteoblast activities in SFs from patients with a loose joint prosthesis and periprosthetic osteolysis as well as in SFs from patients with OA. SF-induced bone resorption was dependent on activation of the RANKL/RANK/OPG pathway. The bone-resorbing activity could not be attributed solely to any of the known pro-inflammatory cytokines, well known to stimulate bone resorption, or to RANKL or prostaglandin E2 in SFs. The data indicate that SFs from patients with a loose prosthesis or with OA stimulate bone resorption and that SFs from patients with OA are more prone to enhance bone formation.
authors.affiliation: Department of Orthopaedic Surgery, Karolinska Hospital, Karolinska Institute, 171 76, Stockholm, Sweden. martin.andersson.502@student.ki.se
authors.forename: Martin K
authors.initials: MK
authors.lastname: Andersson
authors.forename: Pernilla
authors.initials: P
authors.lastname: Lundberg
authors.forename: Acke
authors.initials: A
authors.lastname: Ohlin
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Perry
authors.forename: Anita
authors.initials: A
authors.lastname: Lie
authors.forename: André
authors.initials: A
authors.lastname: Stark
authors.forename: Ulf H
authors.initials: UH
authors.lastname: Lerner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D006801:Humans; D007595:Joint Prosthesis; D051379:Mice; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology; D011475:Prosthesis Failure; D012886:Skull / Q000166:cytology / Q000378:metabolism*; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism*