{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:47:01Z","timestamp":1790016421588,"version":"4.0.1"},"reference-count":41,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:00:00Z","timestamp":1708992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011033","name":"European Union","doi-asserted-by":"publisher","award":["SAF2017-85806-R"],"award-info":[{"award-number":["SAF2017-85806-R"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"European Union","doi-asserted-by":"publisher","award":["PID2021-124890OB-I00"],"award-info":[{"award-number":["PID2021-124890OB-I00"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gouty arthritis results from monosodium urate (MSU) crystal deposition in joints, initiating (pro)-interleukin (IL)-1\u03b2 maturation, inflammatory mediator release, and neutrophil infiltration, leading to joint swelling and pain. Parathyroid hormone-related protein (107\u2013111) C-terminal peptide (osteostatin) has shown anti-inflammatory properties in osteoblasts and collagen-induced arthritis in mice, but its impact in gouty arthritis models remains unexplored. We investigated the effect of osteostatin on pyroptosis, inflammation, and oxidation in macrophages, as well as its role in the formation of calcium pyrophosphate dihydrate crystals and MSU-induced gouty arthritis in mice models. Osteostatin ameliorated pyroptosis induced by lipopolysaccharide and adenosine 5\u2032-triphosphate (LPS + ATP) in mice peritoneal macrophages by reducing the expression of caspase-1, lactate dehydrogenase release, and IL-1\u03b2 and IL-18 secretion. Additionally, IL-6 and tumor necrosis factor-\u03b1 (TNF-\u03b1) were also decreased due to the reduced activation of the NF-\u03baB pathway. Furthermore, osteostatin displayed antioxidant properties in LPS + ATP-stimulated macrophages, resulting in reduced production of mitochondrial and extracellular reactive oxygen species and enhanced Nrf2 translocation to the nuclei. In both models of gouty arthritis, osteostatin administration resulted in reduced pro-inflammatory cytokine production, decreased leukocyte migration, and reduced caspase-1 and NF-\u03baB activation. These results highlight the potential of osteostatin as a therapeutic option for gouty arthritis.<\/jats:p>","DOI":"10.3390\/ijms25052752","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T11:52:55Z","timestamp":1709034775000},"page":"2752","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Osteostatin Mitigates Gouty Arthritis through the Inhibition of Caspase-1 Activation and Upregulation of Nrf2 Expression"],"prefix":"10.3390","volume":"25","author":[{"given":"Laura","family":"Catal\u00e1n","sequence":"first","affiliation":[{"name":"Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM), University of Valencia, Av. Vicent Andr\u00e9s Estell\u00e9s s\/n, 46100 Burjassot, Spain"},{"name":"Department of Pharmacology, Faculty of Pharmacy and Food Sciences, University of Valencia, Av. Vicent Andr\u00e9s Estell\u00e9s s\/n, 46100 Burjassot, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Carmen","family":"Carceller","sequence":"additional","affiliation":[{"name":"Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM), University of Valencia, Av. Vicent Andr\u00e9s Estell\u00e9s s\/n, 46100 Burjassot, Spain"},{"name":"Department of Pharmacy, Pharmaceutical Technology and Parasitology, Faculty of Pharmacy and Food Sciences, University of Valencia, Av. Vicent Andr\u00e9s Estell\u00e9s s\/n, 46100 Burjassot, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3800-6048","authenticated-orcid":false,"given":"Mar\u00eda Carmen","family":"Terencio","sequence":"additional","affiliation":[{"name":"Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM), University of Valencia, Av. Vicent Andr\u00e9s Estell\u00e9s s\/n, 46100 Burjassot, Spain"},{"name":"Department of Pharmacology, Faculty of Pharmacy and Food Sciences, University of Valencia, Av. Vicent Andr\u00e9s Estell\u00e9s s\/n, 46100 Burjassot, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5459-6407","authenticated-orcid":false,"given":"Mar\u00eda Jos\u00e9","family":"Alcaraz","sequence":"additional","affiliation":[{"name":"Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM), University of Valencia, Av. Vicent Andr\u00e9s Estell\u00e9s s\/n, 46100 Burjassot, Spain"},{"name":"Department of Pharmacology, Faculty of Pharmacy and Food Sciences, University of Valencia, Av. Vicent Andr\u00e9s Estell\u00e9s s\/n, 46100 Burjassot, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4059-0175","authenticated-orcid":false,"given":"Mar\u00eda Luisa","family":"Ferr\u00e1ndiz","sequence":"additional","affiliation":[{"name":"Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM), University of Valencia, Av. Vicent Andr\u00e9s Estell\u00e9s s\/n, 46100 Burjassot, Spain"},{"name":"Department of Pharmacology, Faculty of Pharmacy and Food Sciences, University of Valencia, Av. Vicent Andr\u00e9s Estell\u00e9s s\/n, 46100 Burjassot, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1801-311X","authenticated-orcid":false,"given":"Mar\u00eda Carmen","family":"Montesinos","sequence":"additional","affiliation":[{"name":"Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM), University of Valencia, Av. Vicent Andr\u00e9s Estell\u00e9s s\/n, 46100 Burjassot, Spain"},{"name":"Department of Pharmacology, Faculty of Pharmacy and Food Sciences, University of Valencia, Av. Vicent Andr\u00e9s Estell\u00e9s s\/n, 46100 Burjassot, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"key":"ref_1","unstructured":"Fenando, A., Rednam, M., Gujarathi, R., and Widrich, J. (2023, September 26). Gout. 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