{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T13:25:36Z","timestamp":1774963536085,"version":"3.50.1"},"reference-count":54,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T00:00:00Z","timestamp":1693440000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Osteomyelitis is a pathological condition of the bone, frequently associated with the presence of infectious agents \u2013 namely\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    \u2013 that induce inflammation and tissue destruction. Recent advances in the understanding of its pathophysiology and the identification of innovative therapeutic approaches were gathered from experimental in vitro and in vivo systems. However, cell culture models offer limited representativeness of the cellular functionality and the cell\u2013cell and cell\u2010matrix interactions, further failing to mimic the three\u2010dimensional tissue organization; and animal models allow for limited mechanistic assessment given the complex nature of systemic and paracrine regulatory systems and are endorsed with ethical constraints. Accordingly, this study aims at the establishment and assessment of a new ex vivo bone infection model, upon the organotypic culture of embryonic chicken femurs colonized with\n                    <jats:italic>S. aureus<\/jats:italic>\n                    , highlighting the model responsiveness at the molecular, cellular, and tissue levels. Upon infection with distinct bacterial inoculums, data reported an initial exponential bacterial growth, followed by diminished metabolic activity. At the tissue level, evidence of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    \u2010mediated tissue destruction was attained and demonstrated through distinct methodologies, conjoined with decreased osteoblastic\/osteogenic and increased osteoclastic\/osteoclastogenic functionalities\u2014representative of the osteomyelitis clinical course. Overall, the establishment and characterization of an innovative bone tissue infection model that is simple, reproducible, easily manipulated, cost\u2010effective, and simulates many features of human osteomyelitis, further allowing the maintenance of the bone tissue's three\u2010dimensional morphology and cellular arrangement, was achieved. Model responsiveness was further demonstrated, showcasing the capability to improve the research pipeline in bone tissue infection\u2010related research.\n                  <\/jats:p>","DOI":"10.1096\/fj.202300287rr","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T14:57:50Z","timestamp":1693493870000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrative tissue, cellular and molecular responsiveness of an innovative ex vivo model of the\n                    <i>Staphylococcus aureus<\/i>\n                    \u2010mediated bone infection"],"prefix":"10.1096","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5908-1437","authenticated-orcid":false,"given":"Lorena Castro","family":"Mariano","sequence":"first","affiliation":[{"name":"BoneLab\u2013Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine University of Porto  Porto Portugal"},{"name":"LAQV\/REQUIMTE University of Porto  Porto Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9476-2839","authenticated-orcid":false,"given":"Liliana","family":"Grenho","sequence":"additional","affiliation":[{"name":"BoneLab\u2013Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine University of Porto  Porto Portugal"},{"name":"LAQV\/REQUIMTE University of Porto  Porto Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9391-9574","authenticated-orcid":false,"given":"Maria Helena","family":"Fernandes","sequence":"additional","affiliation":[{"name":"BoneLab\u2013Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine University of Porto  Porto Portugal"},{"name":"LAQV\/REQUIMTE University of Porto  Porto Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5365-2123","authenticated-orcid":false,"given":"Pedro","family":"de Sousa\u00a0Gomes","sequence":"additional","affiliation":[{"name":"BoneLab\u2013Laboratory for Bone 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