{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T05:02:43Z","timestamp":1788670963532,"version":"build-2803163510"},"reference-count":73,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T00:00:00Z","timestamp":1684108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 Research and Innovation Program","award":["No. 739582"],"award-info":[{"award-number":["No. 739582"]}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Program","award":["No. 664620"],"award-info":[{"award-number":["No. 664620"]}]},{"name":"European Regional Development Fund through the \u201cScience and Education for Smart Growth\u201d Operational Program","award":["No. 739582"],"award-info":[{"award-number":["No. 739582"]}]},{"name":"European Regional Development Fund through the \u201cScience and Education for Smart Growth\u201d Operational Program","award":["No. 664620"],"award-info":[{"award-number":["No. 664620"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The synthetic 2-cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) is a potent activator of the erythroid 2-p45-derived factor 2, Nrf2, a leucine-zipper regulator of the antioxidant response. Herein, we investigated the effect of CDDO-Me on neutrophil function in a murine model of joint damage. Collagenase-induced osteoarthritis (CIOA) was initiated by the intra-articular injection of collagenase in the knee-joint cavity of Balb\/c mice. CDDO-Me was administrated intra-articularly twice a week starting at day 7 post-CIOA, and its effect was evaluated at day 14. Neutrophils in blood and bone marrow (BM), cell apoptosis, necrosis, expression of C-X-C chemokine receptor 4 (CXCR4), beta-galactosidase (\u03b2-Gal), and Nrf2 levels were measured by flow cytometry. In vitro, CDDO-Me promoted cell survival, reduced cell necrosis, and increased Nrf2 levels by 1.6 times. It decreased surface CXCR4 expression and reduced the frequency of senescent \u03b2-Gal+CXCR4+ neutrophils by three times. In vivo, the degree of knee-joint damage in CIOA was correlated with upregulated CXCR4 on CD11b+ neutrophils. CDDO-Me improved the disease histological score, increased the levels of Nrf2, and downregulated surface CXCR4 on mature BM cells. Our data suggest that CDDO-Me may act as a potent regulator of neutrophil senescence during the progression of knee-joint damage.<\/jats:p>","DOI":"10.3390\/ijms24108775","type":"journal-article","created":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T02:37:51Z","timestamp":1684204671000},"page":"8775","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Triterpenoid Nrf2 Activator, CDDO-Me, Decreases Neutrophil Senescence in a Murine Model of Joint Damage"],"prefix":"10.3390","volume":"24","author":[{"given":"Kristiana M.","family":"Amirova","sequence":"first","affiliation":[{"name":"Laboratory of Metabolomics, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 4000 Plovdiv, Bulgaria"},{"name":"Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0920-3712","authenticated-orcid":false,"given":"Petya A.","family":"Dimitrova","sequence":"additional","affiliation":[{"name":"Department of Immunology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7370-2383","authenticated-orcid":false,"given":"Milena N.","family":"Leseva","sequence":"additional","affiliation":[{"name":"Department of Immunology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivanka K.","family":"Koycheva","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolomics, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 4000 Plovdiv, Bulgaria"},{"name":"Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0316-9859","authenticated-orcid":false,"given":"Albena T.","family":"Dinkova-Kostova","sequence":"additional","affiliation":[{"name":"Division of Cellular and Systems Medicine, School of Medicine, University of Dundee, Dundee DD1 9SY, UK"},{"name":"Department of Medicine and Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5248-6135","authenticated-orcid":false,"given":"Milen I.","family":"Georgiev","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolomics, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 4000 Plovdiv, Bulgaria"},{"name":"Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/nrm2233","article-title":"Cellular senescence: When bad things happen to good cells","volume":"8","author":"Campisi","year":"2007","journal-title":"Nat. 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