{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T12:31:50Z","timestamp":1777033910913,"version":"3.51.4"},"reference-count":64,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["DFG RE 3304\/12-1"],"award-info":[{"award-number":["DFG RE 3304\/12-1"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["NE 1932\/1-3"],"award-info":[{"award-number":["NE 1932\/1-3"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["RE 3304\/9-1"],"award-info":[{"award-number":["RE 3304\/9-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bone fracture activates the immune system and induces inflammation crucial for fracture healing but may also affect trauma-distant organs like the liver. Acute alcohol intoxication (AAI) dysregulates immune responses and affects organ damage post-trauma. However, the bone\u2013liver axis and alcohol\u2019s role in this process remain poorly understood. This study explores liver inflammation and damage following fracture, with and without prior AAI. Twenty-four male C57BL\/6J mice were randomly assigned to four groups (n = 6) and received either NaCl (control) or 35% ethanol via gavage. Mice underwent femur osteotomy with external fixation or sham surgery. After 24 h, liver damage was assessed using hematoxylin\u2013eosin and activated caspase-3 staining. Liver inflammation was evaluated through CXCL1 and polymorphonuclear leukocyte (PMNL) immunostaining, cytokine gene and protein expression analyses, and immune cell profiling in the liver via flow cytometry. Western blotting assessed NF-\u03baB and Wnt signaling. Neither fracture alone nor with AAI caused significant liver damage. However, fracture significantly increased PMNL infiltration and altered monocyte populations, effects that were amplified by AAI. The hepatic neutrophil-to-monocyte ratio significantly decreased after fracture and was absent in the fracture AAI group. CXCL1 increased post-fracture, while MCP-1 and IL-10 decreased significantly, with AAI further significantly amplifying these changes. Wnt1 and Wnt3a levels increased significantly after fracture and were further strongly elevated by AAI. AAI completely abolished fracture-induced significant \u03b2-catenin reduction and significantly increased its phosphorylation, effects that potentially involve an AAI-induced \u03b2-catenin stabilization as well as its increased degradation. NF-\u03baB activation was significantly decreased, while A20 expression significantly increased after fracture and AAI. Fracture influences the inflammatory liver response and signaling pathways, effects which were further modulated by AAI.<\/jats:p>","DOI":"10.3390\/ijms26104923","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T04:05:17Z","timestamp":1747800317000},"page":"4923","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploring the Bone\u2013Liver Axis: Impact of Acute Ethanol Intoxication on Post-Traumatic Liver Inflammation and Damage Following Femur Fracture"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0671-7698","authenticated-orcid":false,"given":"Jasmin Maria","family":"B\u00fclow","sequence":"first","affiliation":[{"name":"Department of Trauma, Hand, Plastic and Reconstructive Surgery, Translational and Experimental Trauma Research, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9311-0131","authenticated-orcid":false,"given":"Helen","family":"Rinderknecht","sequence":"additional","affiliation":[{"name":"Department of Trauma, Hand, Plastic and Reconstructive Surgery, Translational and Experimental Trauma Research, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nils","family":"Becker","sequence":"additional","affiliation":[{"name":"Department of Trauma, Hand, Plastic and Reconstructive Surgery, Translational and Experimental Trauma Research, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kernt","family":"K\u00f6hler","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Pathology, Justus Liebig University Giessen, 35390 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessa","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Trauma, Hand, Plastic and Reconstructive Surgery, Translational and Experimental Trauma Research, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuntao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Trauma, Hand, Plastic and Reconstructive Surgery, Translational and Experimental Trauma Research, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5256-3732","authenticated-orcid":false,"given":"Katrin","family":"Bundkirchen","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Department of Trauma Surgery, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8537-2238","authenticated-orcid":false,"given":"Claudia","family":"Neunaber","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Department of Trauma Surgery, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5625-8823","authenticated-orcid":false,"given":"Borna","family":"Relja","sequence":"additional","affiliation":[{"name":"Department of Trauma, Hand, Plastic and Reconstructive Surgery, Translational and Experimental Trauma Research, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e580","DOI":"10.1016\/S2666-7568(21)00172-0","article-title":"Global, regional, and national burden of bone fractures in 204 countries and territories, 1990\u20132019: A systematic analysis from the Global Burden of Disease Study 2019","volume":"2","author":"Wu","year":"2021","journal-title":"Lancet Healthy Longev."},{"key":"ref_2","unstructured":"WHO (2024). 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