title: Polyethylene particle-induced bone resorption in substance P-deficient mice.
abstract: Aseptic loosening is the major cause of total joint replacement failure. Substance P (SP) is a neurotransmitter richly distributed in sensory nerve fibers, bone, and bone-related tissue. The purpose of this study was to investigate the potential impact of SP on bone metabolism in polyethylene particle-induced osteolysis. We utilized the murine calvarial osteolysis model based on ultrahigh molecular weight polyethylene (UHMWPE) particles in 14 wild-type mice (C57BL/J6) and 14 SP-deficient mice. Group 1 (C57BL/J 6) and group 3 (SP-knockout) received sham surgery, and group 2 (C57BL/J6) and group 4 (SP-knockout) were treated with polyethylene particles. Analytical methods included three-dimensional micro-computed tomographic (micro-CT) analysis and histomorphometry. Bone resorption was measured within the midline suture. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase-positive cells. UHMWPE-particle treated SP-deficient mice showed significantly reduced osteolysis compared to wild-type mice, as confirmed by histomorphometry (P < 0.001) and micro-CT (P = 0.035). Osteoclast numbers were significantly reduced in groups 3 and 4 compared to groups 1 and 2 (P < 0.001). Unexpectedly, SP-deficient mice (group 3) showed a significantly increased absolute bone mass compared to wild-type mice (group 1) (P = 0.02). The findings of our murine calvaria model lead to the assumption that SP is a promoter in particle-induced osteolysis. The pathophysiology of aseptic loosening is complex, and neuropeptides are not solely responsible for the progress of implant loosening; however, we conclude that there could be coherence between neurotransmitters and particle-induced osteolysis in patients with aseptic loosening.
authors.affiliation: Department of Orthopedics, University of Duisburg-Essen, Pattbergstrasse 1-3, 45239, Essen, Germany. christian.wedemeyer@uni-duisburg-essen.de
authors.forename: C
authors.initials: C
authors.lastname: Wedemeyer
authors.forename: C
authors.initials: C
authors.lastname: Neuerburg
authors.forename: A
authors.initials: A
authors.lastname: Pfeiffer
authors.forename: A
authors.initials: A
authors.lastname: Heckelei
authors.forename: F
authors.initials: F
authors.lastname: von Knoch
authors.forename: G
authors.initials: G
authors.lastname: Hilken
authors.forename: J
authors.initials: J
authors.lastname: Brankamp
authors.forename: F
authors.initials: F
authors.lastname: Henschke
authors.forename: M
authors.initials: M
authors.lastname: von Knoch
authors.forename: F
authors.initials: F
authors.lastname: Löer
authors.forename: G
authors.initials: G
authors.lastname: Saxler
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced* / Q000000981:diagnostic imaging; D001842:Bone and Bones / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053758:Nanoparticles / Q000627:therapeutic use*; D010020:Osteonecrosis / Q000188:drug therapy* / Q000473:pathology; D011095:Polyethylenes / Q000494:pharmacology / Q000627:therapeutic use*; D011475:Prosthesis Failure; D012886:Skull / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D013373:Substance P / Q000235:genetics* / Q000494:pharmacology; D014057:Tomography, X-Ray Computed
chemical_list: D011095:Polyethylenes; C111601:ultra-high molecular weight polyethylene; D013373:Substance P