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Polyethylene Particle-Induced Bone Resorption in Substance P-Deficient Mice

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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.

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Acknowledgments

The study was supported by Biomaterialien/Ministerium für Forschung und Wissenschaft and IFORES/University of Duisburg-Essen. The authors thank Kaye Schreyer and Bettina Drawe for editorial assistance with the manuscript, Sylvia Marks for technical assistance during histological and immunohistochemical processing of the specimens, and Prof. Iliakis for advice regarding histomorphometry and microscopy.

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Authors and Affiliations

  1. Department of Orthopedics, University of Duisburg-Essen, Pattbergstrasse 1-3, 45239, Essen, Germany

    C. Wedemeyer, C. Neuerburg, A. Pfeiffer, A. Heckelei, J. Brankamp, M. von Knoch, F. Löer & G. Saxler

  2. Department of Orthopedic Surgery, Schulthess Clinic, Lengghalde 2, 8008, Zürich, Switzerland

    F. von Knoch

  3. Central Animal Laboratory, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany

    G. Hilken

  4. Pathologisches Institut am Johannisstift, Reumontstrasse 28, 33102, Paderborn, Germany

    F. Henschke

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  1. C. Wedemeyer
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Correspondence to C. Wedemeyer.

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Wedemeyer, C., Neuerburg, C., Pfeiffer, A. et al. Polyethylene Particle-Induced Bone Resorption in Substance P-Deficient Mice. Calcif Tissue Int 80, 268–274 (2007). https://doi.org/10.1007/s00223-007-9005-5

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  • DOI: https://doi.org/10.1007/s00223-007-9005-5

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