Polyethylene particle-induced bone resorption in alpha-calcitonin gene-related peptide-deficient mice.
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Polyethylene particle-induced bone resorption in alpha-calcitonin gene-related peptide-deficient mice. / Wedemeyer, Christian; Neuerburg, Carl; Pfeiffer, Anne; Heckelei, Anja; Bylski, David; von Knoch, Fabian; Schinke, Thorsten; Hilken, Gero; Gosheger, Georg; von Knoch, Marius; Löer, Franz; Saxler, Guido.
in: J BONE MINER RES, Jahrgang 22, Nr. 7, 7, 2007, S. 1011-1019.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Polyethylene particle-induced bone resorption in alpha-calcitonin gene-related peptide-deficient mice.
AU - Wedemeyer, Christian
AU - Neuerburg, Carl
AU - Pfeiffer, Anne
AU - Heckelei, Anja
AU - Bylski, David
AU - von Knoch, Fabian
AU - Schinke, Thorsten
AU - Hilken, Gero
AU - Gosheger, Georg
AU - von Knoch, Marius
AU - Löer, Franz
AU - Saxler, Guido
PY - 2007
Y1 - 2007
N2 - This study investigates the impact of alpha-CGRP on bone metabolism after implantation of polyethylene particles. alpha-CGRP knockout mice showed less osteolysis compared with wildtype mice. The local neurogenic microenvironment might be a crucial factor in particle-induced osteolysis. INTRODUCTION: Periprosthetic osteolysis is the major reason for aseptic loosening in joint arthroplasty. This study aimed to investigate the potential impact of alpha-calcitonin gene-related peptide (alpha-CGRP) deficiency on bone metabolism under conditions of polyethylene particle-induced osteolysis. MATERIALS AND METHODS: We used the murine calvarial osteolysis model based on polyethylene particles in 14 C57BL 6 mice and 14 alpha-CGRP-deficient mice divided into four groups of 7 mice each. Groups 1 (C57BL/J 6) and 3 (alpha-CGRP knockout) received sham surgery, and groups 2 (C57BL/J 6) and 4 (alpha-CGRP knockout) were treated with polyethylene particles. Qualitative and quantitative 3D analyses were performed using microCT. In addition, bone resorption was measured within the midline suture by histological examination. The number of osteoclasts was determined by counting the TRACP(+) cells. Calvarial bone was tested for RANKL expression by RT-PCR and immunocytochemistry. RESULTS: Bone resorption was significantly reduced in alpha-CGRP-deficient mice compared with their corresponding wildtype C57BL 6 mice as confirmed by histomorphometric data (p <0.001) and microCT (p <0.01). Osteoclast numbers were significantly reduced in group 3 and the particle subgroup compared with group 1 (p <0.001). We observed a >3-fold increase of basal RANKL mRNA levels within group 1 compared with group 3. Additional low RANKL immunochemistry staining was noted in groups 3 and 4. CONCLUSIONS: In conclusion, alpha-CGRP knockout mice did not show the expected extended osteolysis compared with wildtype mice expressing alpha-CGRP. One of the most reasonable explanations for the observed decrease in osteolysis could be linked to the osteoprotegerin (OPG)/RANK/RANKL system in alpha-CGRP-deficient animals. As a consequence, the fine tuning of osteoclasts mediating resorption in alpha-CGRP-null mice may be deregulated.
AB - This study investigates the impact of alpha-CGRP on bone metabolism after implantation of polyethylene particles. alpha-CGRP knockout mice showed less osteolysis compared with wildtype mice. The local neurogenic microenvironment might be a crucial factor in particle-induced osteolysis. INTRODUCTION: Periprosthetic osteolysis is the major reason for aseptic loosening in joint arthroplasty. This study aimed to investigate the potential impact of alpha-calcitonin gene-related peptide (alpha-CGRP) deficiency on bone metabolism under conditions of polyethylene particle-induced osteolysis. MATERIALS AND METHODS: We used the murine calvarial osteolysis model based on polyethylene particles in 14 C57BL 6 mice and 14 alpha-CGRP-deficient mice divided into four groups of 7 mice each. Groups 1 (C57BL/J 6) and 3 (alpha-CGRP knockout) received sham surgery, and groups 2 (C57BL/J 6) and 4 (alpha-CGRP knockout) were treated with polyethylene particles. Qualitative and quantitative 3D analyses were performed using microCT. In addition, bone resorption was measured within the midline suture by histological examination. The number of osteoclasts was determined by counting the TRACP(+) cells. Calvarial bone was tested for RANKL expression by RT-PCR and immunocytochemistry. RESULTS: Bone resorption was significantly reduced in alpha-CGRP-deficient mice compared with their corresponding wildtype C57BL 6 mice as confirmed by histomorphometric data (p <0.001) and microCT (p <0.01). Osteoclast numbers were significantly reduced in group 3 and the particle subgroup compared with group 1 (p <0.001). We observed a >3-fold increase of basal RANKL mRNA levels within group 1 compared with group 3. Additional low RANKL immunochemistry staining was noted in groups 3 and 4. CONCLUSIONS: In conclusion, alpha-CGRP knockout mice did not show the expected extended osteolysis compared with wildtype mice expressing alpha-CGRP. One of the most reasonable explanations for the observed decrease in osteolysis could be linked to the osteoprotegerin (OPG)/RANK/RANKL system in alpha-CGRP-deficient animals. As a consequence, the fine tuning of osteoclasts mediating resorption in alpha-CGRP-null mice may be deregulated.
M3 - SCORING: Zeitschriftenaufsatz
VL - 22
SP - 1011
EP - 1019
JO - J BONE MINER RES
JF - J BONE MINER RES
SN - 0884-0431
IS - 7
M1 - 7
ER -