title: The role of calcitonin receptor signalling in polyethylene particle-induced osteolysis.
abstract: The detection of peptides from the calcitonin (CT) family in the periarticular tissue of loosened implants has raised hopes of opening new regenerative therapies in the process of aseptic loosening, which remains the major cause of early implant failure in endoprosthetic surgery. We have previously shown the roles of α-calcitonin gene-related peptide (α-CGRP) and the CALCA gene which encodes α-CGRP/CT in this process. To uncover the role of direct calcitonin receptor (CTR) mediated signalling, we studied particle-induced osteolysis (PIO) in a murine calvaria model with a global deletion of the CTR (CTR-KO) using μCT analysis and histomorphometry. As expected, CTR-KO mice revealed reduced bone volume compared to wild-type (WT) controls (p<0.05). In CTR-KO mice we found significantly higher RANKL (receptor activator of NF-κB ligand) expression in the particle group than in the control group. The increase in osteoclast numbers by the particles was twice as high as the increase of osteoclasts in the WT mice (400 vs. 200%). Changes in the eroded surface and actual osteolysis due to ultrahigh-molecular-weight polyethylene particles were similar in WTs and CTR-KOs. Taken together, our findings strengthen the relevance of the OPG/RANK/RANKL system in the PIO process. CTR seems to have an effect on osteoclast differentiation in this context. As there were no obvious changes of the amount of PIO in CTR deficiency, regenerative strategies in aseptic loosening of endoprosthetic implants based on peptides arising from the CT family should rather focus on the impact of α-CGRP.
authors.affiliation: Experimental Surgery and Regenerative Medicine, Department of Trauma Surgery - Campus Innenstadt, Munich University Hospital LMU, Munich, Germany. Electronic address: carl.neuerburg@med.uni-muenchen.de.
authors.forename: Carl
authors.initials: C
authors.lastname: Neuerburg
authors.affiliation: Department of Orthopedics, University Hospital, University of Duisburg-Essen, Essen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Wedemeyer
authors.affiliation: Department of Orthopedics, University Hospital, University of Duisburg-Essen, Essen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Goedel
authors.affiliation: Department of Orthopedics, University Hospital, University of Duisburg-Essen, Essen, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Schlepper
authors.affiliation: Central Animal Laboratory, University Hospital, University of Duisburg-Essen, Essen, Germany.
authors.forename: Gero
authors.initials: G
authors.lastname: Hilken
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital, University of Duisburg-Essen, Essen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Schwindenhammer
authors.affiliation: Experimental Plastic Surgery, Clinic for Plastic and Hand Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Arndt Friedrich
authors.initials: AF
authors.lastname: Schilling
authors.affiliation: Department of Orthopedics, University Hospital, University of Duisburg-Essen, Essen, Germany; Department of Trauma Surgery, University Hospital, University of Duisburg-Essen, Essen, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Jäger
authors.affiliation: Department of Trauma Surgery, University Hospital, University of Duisburg-Essen, Essen, Germany.
authors.forename: Max Daniel
authors.initials: MD
authors.lastname: Kauther
mesh_terms: D000818:Animals; D002452:Cell Count; D003404:Creatinine / Q000652:urine; D021621:Imaging, Three-Dimensional; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D015675:Osteocalcin / Q000378:metabolism; D010010:Osteoclasts / Q000473:pathology; D010014:Osteolysis / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000652:urine; D053244:Osteoprotegerin / Q000378:metabolism; D020959:Polyethylene / Q000009:adverse effects*; D053245:RANK Ligand / Q000378:metabolism; D018003:Receptors, Calcitonin / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction; D012886:Skull / Q000000981:diagnostic imaging / Q000473:pathology; D055114:X-Ray Microtomography
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; D018003:Receptors, Calcitonin; D015675:Osteocalcin; D020959:Polyethylene; D003404:Creatinine
keywords: Aseptic loosening; Calcitonin receptor; OPG; RANKL; UHMWPE