title: Contribution of human osteoblasts and macrophages to bone matrix degradation and proinflammatory cytokine release after exposure to abrasive endoprosthetic wear particles.
abstract: One of the major reasons for failure after total joint arthroplasty is aseptic loosening of the implant. At articulating surfaces, defined as the interface between implant and surrounding bone cement, wear particles can be generated and released into the periprosthetic tissue, resulting in inflammation and osteolysis. The aim of the present study was to evaluate the extent to which osteoblasts and macrophages are responsible for the osteolytic and inflammatory reactions following contact with generated wear particles from Ti‑6Al‑7Nb and Co‑28Cr‑6Mo hip stems. To this end, human osteoblasts and THP‑1 monocytic cells were incubated with the experimentally generated wear particles as well as reference particles (0.01 and 0.1 mg/ml) for 48 h under standard culture conditions. To evaluate the impact of these particles on the two cell types, the release of different bone matrix degrading matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), and relevant cytokines were determined by multiplex enzyme‑linked immunosorbent assays. Following incubation with wear particles, human osteoblasts showed a significant upregulation of MMP1 and MMP8, whereas macrophages reacted with enhanced MMP3, MMP8 and MMP10 production. Moreover, the synthesis of TIMPs 1 and 2 was inhibited. The osteoblasts and macrophages also responded with modified expression of the inflammatory mediators interleukin (IL)‑6, IL‑8, monocyte chemoattractant protein‑1 and vascular endothelial growth factor. These results demonstrate that the release of wear particles affects the release of proinflammatory cytokines and has a negative impact on bone matrix formation during the first 48 h of particle exposure. Human osteoblasts are directly involved in the proinflammatory cascade of bone matrix degradation. The simultaneous activation and recruitment of monocytes/macrophages boosted osteolytic processes in the periprosthetic tissue. By the downregulation of TIMP production and the concomitant upregulation of MMPs as a response to particle exposure, bone formation around implants may be suppressed, resulting in implant failure.
authors.affiliation: Department of Orthopedics, Biomechanics and Implant Technology Research Laboratory, University Medical Center Rostock, Rostock 18057, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Jonitz-Heincke
authors.affiliation: Department of Orthopedics, Biomechanics and Implant Technology Research Laboratory, University Medical Center Rostock, Rostock 18057, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Lochner
authors.affiliation: Department of Orthopedics, Biomechanics and Implant Technology Research Laboratory, University Medical Center Rostock, Rostock 18057, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schulze
authors.affiliation: Department of Immunology, University Medical Center Rostock, Rostock 18057, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Pohle
authors.affiliation: Department of Orthopedics, Biomechanics and Implant Technology Research Laboratory, University Medical Center Rostock, Rostock 18057, Germany.
authors.forename: Wera
authors.initials: W
authors.lastname: Pustlauk
authors.affiliation: Department of Orthopedics, Biomechanics and Implant Technology Research Laboratory, University Medical Center Rostock, Rostock 18057, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Hansmann
authors.affiliation: Department of Orthopedics, Biomechanics and Implant Technology Research Laboratory, University Medical Center Rostock, Rostock 18057, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Bader
mesh_terms: D019643:Arthroplasty, Replacement / Q000009:adverse effects; D001857:Bone Matrix / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D010014:Osteolysis / Q000378:metabolism; D019736:Prostheses and Implants; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases