The role of calcitonin receptor signalling in polyethylene particle-induced osteolysis

Neuerburg, Carl; Wedemeyer, Christian; Goedel, Jan; Schlepper, Rüdiger; Hilken, Gero; Schwindenhammer, Benjamin; Schilling, Arndt F.; Jäger, Markus; Kauther, Max Daniel

doi:10.1016/j.actbio.2014.11.051

Cited by 10 publications

(11 citation statements)

References 33 publications

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“…In addition, the amount of wear particles may have attributed to the extent of osteolysis observed in the UHMWPE and VE-UHMWPE particle-treated mice in the present study compared to the mice in the SHAM group. Thus, as an attempt to provoke a severe inflammatory response and to determine the osteolytic potential of UHMWPE and VE-UHMWPE particles, an extremely high concentration of particles was chosen in the present study, which was adapted to the amount of wear used in previous experiments by our group (18,19). Huang et al treated the calvaria with 1 mg of wear particles, Bichara et al chose a concentration of 3 mg, whereas a 30- to 10-fold higher particle concentration was chosen in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, biomarker analysis of serum α-CGRP showed a continuous increase in α-CGRP levels throughout the experimental duration time in all groups (SHAM, UHMWPE and VE-UHMWPE) and significantly higher α-CGRP levels in the VE-UHMWPE particle-treated mice at the experimental time of 28 days, whereas minor α-CGRP antibody concentrations were detectable for the first time via immunohistochemistry at day 14 in the UHMWPE and VE-UHMWPE particle-treated mice. Recent investigations by our group on haploinsufficient calcitonin receptor knockout mice identified that regenerative strategies in the aseptic loosening of endoprosthetic implants should focus on the impact of α-CGRP-mediated signalling, although previous results have to be considered (18). Thus, experiments on α-CGRP-deficient mice have demonstrated reduced PIO associated with decreased RANKL mRNA levels compared to wild-type controls, presuming a catabolic effect of α-CGRP in particle induced osteolysis (19).…”

Section: Discussionmentioning

confidence: 99%

“…1985). As described previously, a murine calvaria model of UHMWPE particle-induced osteolysis was established using 54 male C57BL/6 mice provided by Charles River Laboratories, Inc. (Sulzfeld, Germany) (17,18). The animals were delivered at the age of 10 weeks and surgery was performed at the age of 12 weeks.…”

Section: Methodsmentioning

confidence: 99%

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Impact of vitamin E-blended UHMWPE wear particles on the osseous microenvironment in polyethylene particle-induced osteolysis

Neuerburg

Loer

Mittlmeier

et al. 2016

International Journal of Molecular Medicine

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Aseptic loosening mediated by wear particle-induced osteolysis (PIO) remains the major cause of implant loosening in endoprosthetic surgery. The development of new vitamin E (α-tocopherol)-blended ultra-high molecular weight polyethylene (VE-UHMWPE) with increased oxidation resistance and improved mechanical properties has raised hopes. Furthermore, regenerative approaches may be opened, as vitamin E supplementation has shown neuroprotective characteristics mediated via calcitonin gene-related peptide (CGRP), which is known to affect bone remodeling in PIO. Therefore, the present study aimed to further clarify the impact of VE-UHMWPE wear particles on the osseous microenvironment and to identify the potential modulatory pathways involved. Using an established murine calvaria model, mice were subjected to sham operation (SHAM group), or treated with UHMWPE or VE-UHMWPE particles for different experimental durations (7, 14 and 28 days; n=6/group). Morphometric analysis by micro-computed tomography detected significant (p<0.01) and comparable signs of PIO in all particle-treated groups, whereas markers of inflammation [tumor necrosis factor (TNF)-α/tartrate resistant acid phosphatase (TRAP) staining] and bone remodeling [Dickkopf-related protein 1 (DKK-1)/osteoprotegerin (OPG)] were most affected in the early stages following surgery. Taking the present data into account, VE-UHMWPE appears to have a promising biocompatibility and increased ageing resistance. According to the α-CGRP serum levels and immunohistochemistry, the impact of vitamin E on neuropeptidergic signaling and its chance for regenerative approaches requires further investigation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Impact of vitamin E-blended UHMWPE wear particles on the osseous microenvironment in polyethylene particle-induced osteolysis

Neuerburg

Loer

Mittlmeier

et al. 2016

International Journal of Molecular Medicine

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“…It was also demonstrated that UTI inhibits LPS-induced TNF-α and subsequent IL-1β and IL-6 induction by macrophages, at least partly, through the suppression of MAPK signalling pathways such as ERK1/2, JNK and p38 in vitro [37,38]. Whether the inflammatory role of UTI is related with NF-κB and MAPKs signalling pathways is unknown.…”

Section: Discussionmentioning

confidence: 99%

Blockade of NF-κB and MAPK pathways by ulinastatin attenuates wear particle-stimulated osteoclast differentiation in vitro and in vivo

Shi

et al. 2016

Bioscience Reports

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Ulinastatin, a urinary trypsin inhibitor (UTI), is widely used to clinically treat lipopolysaccharide (LPS)-related inflammatory disorders recently. Adherent pathogen-associated molecular patterns (PAMPs), of which LPS is the best-studied and classical endotoxin produced by Gram-negative bacteria, act to increase the biological activity of osteopedic wear particles such as polymethyl-methacrylate (PMMA) and titanium particles in cell culture and animal models of implant loosening. The present study was designed to explore the inhibitory effect of UTI on osteoclastogenesis and inflammatory osteolysis in LPS/PMMA-mediated Raw264.7 cells and murine osteolysis models, and investigate the potential mechanism. The in vitro study was divided into the control group, LPS-induced group, PMMA-stimulated group and UTI-pretreated group. UTI (500 or 5000 units/ml) pretreatment was followed by PMMA (0.5 mg/ml) with adherent LPS. The levels of inflammatory mediators including tumour necrosis factor-α (TNF-α), matrixmetallo-proteinases-9 (MMP-9) and interleukin-6 (IL-6), receptor activation of nuclear factor NF-κB (RANK), and cathepsin K were examined and the amounts of phosphorylated I-κB, MEK, JNK and p38 were measured. In vivo study, murine osteolysis models were divided into the control group, PMMA-induced group and UTI-treated group. UTI (500 or 5000 units/kg per day) was injected intraperitoneally followed by PMMA suspension with adherent LPS (2×108 particles/25 μl) in the UTI-treated group. The thickness of interfacial membrane and the number of infiltrated inflammatory cells around the implants were assessed, and bone mineral density (BMD), trabecular number (Tb.N.), trabecular thickness (Tb.Th.), trabecular separation (Tb.Sp.), relative bone volume over total volume (BV/TV) of distal femur around the implants were calculated. Our results showed that UTI pretreatment suppressed the secretion of proinflammatory cytokines including MMP-9, IL-6, TNF-α, RANK and cathepsin K through down-regulating the activity of nuclear factor kappa B (NF-κB) and MAPKs partly in LPS/PMMA-mediated Raw264.7 cells. Finally, UTI treatment decreased the inflammatory osteolysis reaction in PMMA-induced murine osteolysis models. In conclusion, these results confirm the anti-inflammatory potential of UTI in the prevention of particle disease.

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“…It was reported that the mean bone density of lumbar spine and hip site in the osteoporotic patients significantly increased after treating with CT . The mechanism lies in that CT inhibited the osteoclast activity while simultaneously stimulating the osteoblast activity . One the other hand, BMP2, as one well‐known growth factor of TGF‐β superfamily, could up‐regulate Runx2, DLX5 and osteocalcin mRNA expression to improve the osteogenic differentiation of mesenchymal stem cell (MSCs) in osteoporotic patient …”

Section: Introductionmentioning

confidence: 99%

Enhancement of local bone remodeling in osteoporotic rabbits by biomimic multilayered structures on Ti6Al4V implants

Huang

Luo

et al. 2016

J Biomedical Materials Res

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To enhance long-term survival of titanium implants in patients with osteoporosis, chitosan/gelatin multilayers containing bone morphogenetic protein 2(BMP2) and an antiosteoporotic agent of calcitonin (CT) are deposited on the Ti6Al4V (TC4) implants through layer-by-layer (LBL) electrostatic assembly technique. Here, the obtained titanium alloy implant (TC4/LBL/CT/BMP2) can regulate the release of loaded calcitonin and BMP2 agents in a sustaining manner to accelerate the bone formation and simultaneously inhibit bone resorption. In vitro results show that the bone-related cells on TC4/LBL/CT/BMP2 present the lowest production level of tartrate resistant acid phosphatase (TRAP) but the highest (p < 0.05) level of alkaline phosphatase (ALP) activity, osteocalcin production, mineralization capacity and osteoblast-related gene expression among all groups after treatment for 7 or 21 days, respectively. Besides, in vivo studies of micro-CT analysis, routine histological and immunohistochemical analysis also collectively demonstrate that the TC4/LBL/CT/BMP2 implant can dramatically promote the formation and remodeling of new bone in osteoporotic rabbits after implantation for 30 days and 90 days, respectively. In vivo push-out testing further confirms that the TC4/LBL/CT/BMP2 implant has the highest (p < 0.01) interfacial shear strength and favorable bone-implant osseointegration. Overall, this study establishes a simple and profound methodology to fabricate a biofunctional TC4 implant for the treatment of local osteoporotic fractures in vivo. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1437-1451, 2016.

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The role of calcitonin receptor signalling in polyethylene particle-induced osteolysis

Cited by 10 publications

References 33 publications

Impact of vitamin E-blended UHMWPE wear particles on the osseous microenvironment in polyethylene particle-induced osteolysis

Impact of vitamin E-blended UHMWPE wear particles on the osseous microenvironment in polyethylene particle-induced osteolysis

Blockade of NF-κB and MAPK pathways by ulinastatin attenuates wear particle-stimulated osteoclast differentiation in vitro and in vivo

Enhancement of local bone remodeling in osteoporotic rabbits by biomimic multilayered structures on Ti6Al4V implants

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