{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T19:26:42Z","timestamp":1757705202526,"version":"3.40.4"},"reference-count":72,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2014,5,14]],"date-time":"2014-05-14T00:00:00Z","timestamp":1400025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2014,5,14]],"date-time":"2014-05-14T00:00:00Z","timestamp":1400025600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroimmunomodulation"],"published-print":{"date-parts":[[2015]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Objective:&lt;\/i&gt;&lt;\/b&gt; 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. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; 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 \u00b5g\/ml) to establish osteolytic conditions, and simultaneously treated with CGRP (10&lt;sup&gt;-8&lt;\/sup&gt;&lt;smlcap&gt;M&lt;\/smlcap&gt;). Receptor activator of nuclear factor-&amp;#954;B &lt;i&gt;(RANK)&lt;\/i&gt;, RANK ligand &lt;i&gt;(RANKL)&lt;\/i&gt; and tumour necrosis factor &lt;i&gt;(TNF)&lt;\/i&gt;-&lt;i&gt;a&lt;\/i&gt; 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)-1\u00df and IL-6 were quantified in cell culture supernatants by ELISA and Bio-Plex cytokine assay, respectively. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; Activation of macrophage-like cells failed to enhance the production of RANK but led to a dose- and time-dependent increase of &lt;i&gt;TNF&lt;\/i&gt;-&lt;i&gt;a&lt;\/i&gt; mRNA and secreted protein levels of TNF-a, IL-1\u00df and IL-6. Application of CGRP time-dependently suppressed &lt;i&gt;TNF-a&lt;\/i&gt; 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-1\u00df and IL-6. &lt;b&gt;&lt;i&gt;Conclusions:&lt;\/i&gt;&lt;\/b&gt; 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.<\/jats:p>","DOI":"10.1159\/000360988","type":"journal-article","created":{"date-parts":[[2015,1,14]],"date-time":"2015-01-14T07:46:22Z","timestamp":1421221582000},"page":"152-165","source":"Crossref","is-referenced-by-count":16,"title":["Calcitonin Gene-Related Peptide Modulates the Production of Pro-Inflammatory Cytokines Associated with Periprosthetic Osteolysis by THP-1 Macrophage-Like 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