{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T15:08:22Z","timestamp":1788188902561,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T00:00:00Z","timestamp":1673913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regione Puglia","award":["CUPB84I18000540002"],"award-info":[{"award-number":["CUPB84I18000540002"]}]},{"name":"CNR","award":["CUPB84I18000540002"],"award-info":[{"award-number":["CUPB84I18000540002"]}]},{"name":"Research Center of Excellence for Neurodegenerative Diseases and Brain Aging)\u2014University of Bari \u201cAldo Moro\u201d","award":["CUPB84I18000540002"],"award-info":[{"award-number":["CUPB84I18000540002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bone fractures are a widespread clinical event due to accidental falls and trauma or bone fragility; they also occur in association with various diseases and are common with aging. In the search for new therapeutic strategies, a crucial link between irisin and bone fractures has recently emerged. To explore this issue, we subjected 8-week-old C57BL\/6 male mice to tibial fracture, and then we treated them with intra-peritoneal injection of r-Irisin (100 \u00b5g\/kg\/weekly) or vehicle as control. At day 10 post fracture, histological analysis showed a significant reduced expression of inflammatory cytokines as tumor necrosis factor-alpha (TNF\u03b1) (p = 0.004) and macrophage inflammatory protein-alpha (MIP-1\u03b1) (p = 0.015) in the cartilaginous callus of irisin-treated mice compared to controls, supporting irisin\u2019s anti-inflammatory role. We also found increased expressions of the pro-angiogenic molecule vascular endothelial growth factor (VEGF) (p = 0.002) and the metalloproteinase MMP-13 (p = 0.0006) in the irisin-treated mice compared to the vehicle ones, suggesting a myokine involvement in angiogenesis and cartilage matrix degradation processes. Moreover, the bone morphogenetic protein (BMP2) expression was also upregulated (p = 0.002). Taken together, our findings suggest that irisin can contribute to fracture repair by reducing inflammation and promoting vessel invasion, matrix degradation, and bone formation, supporting its possible role as a novel molecule for fracture treatment.<\/jats:p>","DOI":"10.3390\/ijms24031809","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T02:10:32Z","timestamp":1673921432000},"page":"1809","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Irisin Modulates Inflammatory, Angiogenic, and Osteogenic Factors during Fracture Healing"],"prefix":"10.3390","volume":"24","author":[{"given":"Angela","family":"Oranger","sequence":"first","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Zerlotin","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Buccoliero","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Sanesi","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Storlino","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernestina","family":"Schipani","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth Michael","family":"Kozloff","sequence":"additional","affiliation":[{"name":"Departments of Orthopedic Surgery and Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziana","family":"Colaianni","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Colucci","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7121-5899","authenticated-orcid":false,"given":"Maria","family":"Grano","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.otsr.2018.04.015","article-title":"Total hip arthroplasty after failed fixation of a proximal femur fracture: Analysis of 59 cases of intra- and extra-capsular fractures","volume":"104","author":"Morice","year":"2018","journal-title":"Orthop. 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