Polyethylene particle-induced bone resorption in substance P-deficient mice

• Published in: Calcified tissue international 2007-04, Vol.80 (4), p.268-274
• Main Authors: Wedemeyer, C, Neuerburg, C, Pfeiffer, A, Heckelei, A, von Knoch, F, Hilken, G, Brankamp, J, Henschke, F, von Knoch, M, Löer, F, Saxler, G
• Format: Article
• Language: English
• Subjects: Acid phosphatase (tartrate-resistant); Animals; Bone and Bones - anatomy & histology; Bone and Bones - drug effects; Bone and Bones - metabolism; Bone histomorphometry; Bone implants; Bone mass; Bone resorption; Bone Resorption - chemically induced; Bone Resorption - diagnostic imaging; Bone surgery; Bone turnover; Bones; Calvaria; Computed tomography; Joints; Male; Materials Testing; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular weight; Nanoparticles - therapeutic use; Neuropeptides; Neurotransmitters; Osteoclasts; Osteolysis; Osteonecrosis - drug therapy; Osteonecrosis - pathology; Polyethylene; Polyethylenes - pharmacology; Polyethylenes - therapeutic use; Prosthesis Failure; Rodents; Sensory neurons; Skull - diagnostic imaging; Skull - drug effects; Skull - pathology; Substance P; Substance P - genetics; Substance P - pharmacology; Tomography; Tomography, X-Ray Computed; Transplants & implants
• ISSN: 0171-967X; 1432-0827
• DOI: 10.1007/s00223-007-9005-5

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.