{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:50:53Z","timestamp":1787532653083,"version":"build-2736575974"},"reference-count":17,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["899770"],"award-info":[{"award-number":["899770"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2024,2]]},"abstract":"\n Objective<\/jats:title>\n Calcium pyrophosphate (CPP) crystal deposition in the joints is associated with a heterogeneous set of debilitating syndromes characterized by inflammation and pain, for which no effective therapies are currently available. Because we found that the mitochondrial enzyme monoamine oxidase B (MAO\u2010B) plays a fundamental role in promoting inflammatory pathways, this study aims at assessing the efficacy of two clinical\u2010grade inhibitors (iMAO\u2010Bs) in preclinical models of this disease to pave the way for a novel treatment.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We tested our hypothesis in two murine models of CPP\u2010induced arthritis, by measuring cytokine and chemokine levels, along with immune cell recruitment. iMAO\u2010Bs (rasagiline and safinamide) were administered either before or after crystal injection. To elucidate the molecular mechanism, we challenged in vitro primed macrophages with CPP crystals and assessed the impact of iMAO\u2010Bs in dampening proinflammatory cytokines and in preserving mitochondrial function.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Both in preventive and therapeutic in vivo protocols, iMAO\u2010Bs blunted the release of proinflammatory cytokines (interleukin [IL]\u20106 and IL1\u2010\u03b2) and chemokines (CXCL10, CXCL1, CCL2 and CCL5) (n >\u20096 mice\/group). Importantly, they also significantly reduced ankle swelling (50.3% vs 17.1%;\n P<\/jats:italic>\n <\u20090.001 and 23.1%;\n P<\/jats:italic>\n =\u20090.005 for rasagiline and safinamide, respectively). Mechanistically, iMAO\u2010Bs dampened the burst of reactive oxygen species and the mitochondrial dysfunction triggered by CPP crystals in isolated macrophages. Moreover, iMAO\u2010Bs blunted cytokine secretion and NLRP3 inflammasome activation through inhibition of the NF\u2010\u03baB and STAT3 pathways.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n iMAO\u2010Bs dampen inflammation in murine models of crystal\u2010induced arthropathy, thereby uncovering MAO\u2010B as a promising target to treat these diseases.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.42697","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T09:58:59Z","timestamp":1694426339000},"page":"279-284","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Oxidative Stress by the Mitochondrial Monoamine Oxidase B Mediates Calcium Pyrophosphate Crystal\u2013Induced Arthritis"],"prefix":"10.1002","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4198-3221","authenticated-orcid":false,"given":"Francisca C.","family":"Venegas","sequence":"first","affiliation":[{"name":"University of Padua and Fondazione Istituto di Ricerca Pediatrica Citt\u00e0 della Speranza (IRP) Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"S\u00e1nchez\u2010Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"University of Padua and Fondazione Istituto di Ricerca Pediatrica Citt\u00e0 della Speranza (IRP) Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Luisetto","sequence":"additional","affiliation":[{"name":"University of Padua Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Angioni","sequence":"additional","affiliation":[{"name":"University of Padua and Fondazione Istituto di Ricerca Pediatrica Citt\u00e0 della Speranza (IRP) Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Viola","sequence":"additional","affiliation":[{"name":"University of Padua Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Canton","sequence":"additional","affiliation":[{"name":"University of Padua and Fondazione Istituto di Ricerca Pediatrica Citt\u00e0 della Speranza (IRP) Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-018-0078-5"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.00166"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04516"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0441-8"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1883"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2930"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI94584"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13215478"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.07.006"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2435"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110026"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-022-01076-y"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-017-1353-6"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.01.028"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-018-1952-7"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4616"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2022-222387"}],"container-title":["Arthritis 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