title: The induction of CXCR4 expression in human osteoblast-like cells (MG63) by CoCr particles is regulated by the PLC-DAG-PKC pathway.
abstract: BACKGROUND
  Osteolysis which leads to aseptic loosening of implants is a fundamental problem in joint replacement surgery (arthroplasty) and the leading cause for implant failure and revision surgery. Metal (CoCr) particles separated from implants by wear cause osteolysis and the failure of orthopedic implants, but the molecular mechanism is not clear. The chemokine receptor CXCR4 has been shown to play a pivotal role in periprosthetic osteolysis. The aim of this study was to determine which signal transduction pathway (PLC-DAG-PKC or MAPK/ERK) induces CXCR4 expression in osteoblast-like cells (MG63) cells.
  
  
  METHODS
  MG63 and Jurkat cells were stimulated with different amounts of particles (107, 106, and 105) for different time periods (30 min to 24 h), in the presence and absence of specific inhibitors (chelerythrine for the PLC-DAG-PKC pathway and PD98059 for the MAPK/ERK pathway). The expression of CXCR4-specific mRNA was determined by real-time polymerase chain reaction (PCR), and the PKC activity was measured by Western Blot using an antibody specific for PKC-related phosphorylation.
  
  
  RESULTS
  Real-time PCR data showed that CXCR4 mRNA expression in MG63 cells induced by CoCr particles was significantly diminished by the PKC-specific inhibitor chelerythrine. This effect was not observed with the MAPK/ERK inhibitor PD98059. The involvement of PKC was also confirmed by an intensified phosphorylation pattern after stimulation with CoCr particles. In Jurkat cells, none of the inhibitors exhibited any effect.
  
  
  CONCLUSIONS
  The induction of CXCR4-specific mRNA expression in MG63 cells after stimulation with CoCr particles is regulated by the PLC-DAG-PKC pathway and not by the MAPK/ERK pathway. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2326-2332, 2017.
authors: Department of Orthopaedic Surgery, Otto-von-Guericke University, Magdeburg, Germany.
authors: Andreas
authors: A
authors: Drynda
authors: Department of Orthopaedic Surgery, Otto-von-Guericke University, Magdeburg, Germany.
authors: Qiang
authors: Q
authors: Ren
authors: Department of Orthopaedics, University Medical Center, Göttingen, Germany.
authors: Gottfried H
authors: GH
authors: Buchhorn
authors: Department of Orthopaedic Surgery, Otto-von-Guericke University, Magdeburg, Germany.
authors: Christoph H
authors: CH
authors: Lohmann
mesh_terms: D001178:Arthroplasty / Q000009:adverse effects; D000069343:Bone-Implant Interface / Q000473:pathology; D002460:Cell Line; D002858:Chromium Alloys / Q000009:adverse effects* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D061825:Metal-on-Metal Joint Prostheses / Q000009:adverse effects*; D010006:Osteoblasts / Q000473:pathology; D010014:Osteolysis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D019718:Receptors, CXCR4 / Q000096:biosynthesis*
chemical_list: C527276:CXCR4 protein, human; D002858:Chromium Alloys; D019718:Receptors, CXCR4
keywords: arthroplasty; cell-material interactions; cobalt-chromium (alloys); osteolysis; wear debris