High levels of substance P and CGRP in pseudosynovial fluid from patients with aseptic loosening of their hip prosthesis

Qian, Yebin; Zeng, Bingfang; Zhang, Xianlong; Jiang, Yao

doi:10.1080/17453670710015238

Cited by 9 publications

(12 citation statements)

References 26 publications

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“…Neuropeptides, such as α-CGRP have also been detected in the synovial fluid and periarticular tissue of loosened implants which strengthens the impact of the local neurogenic environment in the process of osteolysis and may open new regenerative therapy approaches (14,15). α-CGRP belongs to the calcitonin (CT) peptide family which is a generated analog to calcitonin by alternative splicing of the CALCA gene (16).…”

Section: Introductionmentioning

confidence: 95%

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: Introductionmentioning

confidence: 95%

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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“…Indeed, CGRP has been shown to possess osteogenic properties by downregulating the production of pro-resorptive cytokines and growth factors or preventing osteoclastogenesis and bone resorption [24,25,26,27,28,29,30]. Due to the detection of CGRP-immunoreactive nerve fibres in the periprosthetic membrane and of CGRP in the synovial fluid of patients with aseptic loosening, the neuropeptide is thought to play a role in periprosthetic osteolysis [31,32]. …”

Section: Introductionmentioning

confidence: 99%

Calcitonin Gene-Related Peptide Modulates the Production of Pro-Inflammatory Cytokines Associated with Periprosthetic Osteolysis by THP-1 Macrophage-Like Cells

Jablonski¹,

Kauther

Bachmann

et al. 2014

Neuroimmunomodulation

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Objective: An anti-resorptive impact of the neuropeptide calcitonin gene-related peptide (CGRP) on periprosthetic osteolysis, the leading cause of early prosthesis loosening, has been shown previously. In this study, the impact of CGRP on pro-inflammatory cytokine production associated with periprosthetic osteolysis was analysed using THP-1 macrophage-like cells. Methods: Cells were stimulated with ultra-high-molecular-weight polyethylene (UHMWPE) particles (cell-to-particle ratios of 1:100 and 1:500) and lipopolysaccharides (LPS; 1 µg/ml) to establish osteolytic conditions, and simultaneously treated with CGRP (10^-8M). Receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL) and tumour necrosis factor (TNF)-a mRNA expression were measured by quantitative RT-PCR. RANK protein was detected by Western blot. Secreted protein levels of TNF-a as well as interleukin (IL)-1ß and IL-6 were quantified in cell culture supernatants by ELISA and Bio-Plex cytokine assay, respectively. Results: Activation of macrophage-like cells failed to enhance the production of RANK but led to a dose- and time-dependent increase of TNF-a mRNA and secreted protein levels of TNF-a, IL-1ß and IL-6. Application of CGRP time-dependently suppressed TNF-a mRNA expression induced by low-particle concentrations and LPS, while both particle- and LPS-induced secretion of TNF-a was inhibited. A pronounced inhibitory effect of CGRP on LPS-induced cytokine production at 24 h of incubation was also observed with IL-1ß and IL-6. Conclusions: CGRP shows a time-dependent inhibitory effect on the secretion of osteolysis-associated pro-inflammatory cytokines, indicating an indirect anti-resorptive influence of the neuropeptide on both aseptic prosthesis loosening and bacterially induced bone resorption which might enhance the life time of total joint replacements.

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“…The presence of peptide hormones from the calcitonin family in the periarticular tissue of loosened implants has raised hopes of establishing new regenerative therapies in the process of aseptic loosening [2,3]. CT has long been known for its important role in protecting the skeleton by regulating bone turnover and maintaining calcium homeostasis [25].…”

Section: Discussionmentioning

confidence: 99%

“…The detection of neuropeptides such as a-calcitonin gene-related peptide (a-CGRP) in the synovial fluid and periarticular tissue of loosened implants gives reason to presume an impact in the process of UHMWPE particle-induced osteolysis (PIO) [2,3]. Furthermore, nerve fibers containing peptides arising from the calcitonin (CT) family have been described in the vicinity of arthritic joints in patients with painful osteoarthritis [3,4].…”

Section: Introductionmentioning

confidence: 99%

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

Neuerburg¹,

Wedemeyer

Goedel

et al. 2015

Acta Biomaterialia

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High levels of substance P and CGRP in pseudosynovial fluid from patients with aseptic loosening of their hip prosthesis

Cited by 9 publications

References 26 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

Calcitonin Gene-Related Peptide Modulates the Production of Pro-Inflammatory Cytokines Associated with Periprosthetic Osteolysis by THP-1 Macrophage-Like Cells

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

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