{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:02:44Z","timestamp":1790013764765,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001702","name":"AO Foundation","doi-asserted-by":"publisher","award":["AR2020_05"],"award-info":[{"award-number":["AR2020_05"]}],"id":[{"id":"10.13039\/501100001702","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    has multiple mechanisms to evade the host's immune system and antibiotic treatment. One such mechanism is the invasion of the osteocyte lacuno\u2010canalicular network (OLCN), which may be particularly important in recurrence of infection after debridement and antibiotic therapy. The aim of this study was to develop an ex vivo model to facilitate further study of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    invasion of the OLCN and early\u2010stage testing of antibacterial strategies against bacteria in this niche. The diameter of the canaliculi of non\u2010infected human, sheep, and mouse bones was measured microscopically on Schmorl's picrothionin stained sections, showing a large overlap in canalicular diameter.\n                    <jats:italic>S. aureus<\/jats:italic>\n                    successfully invaded the OLCN in all species in vitro as revealed by presence in osteocyte lacunae in Brown and Brenn\u2010stained sections and by scanning electron microscopy. Murine bones were then selected for further experiments, and titanium pins with either a wild\u2010type or \u0394PBP4 mutant\n                    <jats:italic>S. aureus<\/jats:italic>\n                    USA300 were placed trans\u2010cortically and incubated for 2 weeks in tryptic soy broth. Wild\u2010type\n                    <jats:italic>S. aureus<\/jats:italic>\n                    readily invaded the osteocyte lacunae in mouse bones while the \u0394PBP4 showed a significantly lower invasion of the OLCN (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0005). Bone specimens were then treated with gentamicin, sitafloxacin, R14 bacteriophages, or left untreated. Gentamicin (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0027) and sitafloxacin (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0280) significantly reduced the proportion of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    \u2010occupied lacunae, whilst bacteriophage treatment had no effect. This study shows that\n                    <jats:italic>S. aureus<\/jats:italic>\n                    is able to invade the OLCN in an ex vivo model. This ex vivo model can be used for future early\u2010stage studies before proceeding to in vivo studies.\n                  <\/jats:p>","DOI":"10.1002\/jor.25988","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T03:24:16Z","timestamp":1728444256000},"page":"446-456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Development of an ex vivo model to study\n                    <i>Staphylococcus aureus<\/i>\n                    invasion of the osteocyte lacuno\u2010canalicular network"],"prefix":"10.1002","volume":"43","author":[{"given":"Niels","family":"Vanvelk","sequence":"first","affiliation":[{"name":"AO Research Institute Davos Davos Switzerland"},{"name":"Trauma Research Unit, Department of Surgery, Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"de Mesy Bentley","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research University of Rochester Medical Center Rochester New York USA"},{"name":"Center for Advanced Research Technology (CART) University of Rochester Medical Center Rochester Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H. J.","family":"Verhofstad","sequence":"additional","affiliation":[{"name":"Trauma Research Unit, Department of Surgery, Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4114-9093","authenticated-orcid":false,"given":"Willem\u2010Jan","family":"Metsemakers","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery University Hospitals Leuven Leuven Belgium"},{"name":"Department of Development and Regeneration KU Leuven\u2014University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2307-0397","authenticated-orcid":false,"given":"Thomas F.","family":"Moriarty","sequence":"additional","affiliation":[{"name":"AO Research Institute Davos Davos Switzerland"},{"name":"Center for Muskuloskeletal Infections (ZMSI) University Hospital Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4845-1922","authenticated-orcid":false,"given":"Claudia","family":"Siverino","sequence":"additional","affiliation":[{"name":"AO Research Institute Davos Davos Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24804"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/23744235.2019.1572219"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2017.03.030"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00402-018-3048-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00686-0"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-019-0061-z"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3055"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.CC.17.00154"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/apm.13312"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24230"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.25765"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2019.102039"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008988"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0285770"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-008055232-3.61328-5"},{"key":"e_1_2_9_17_1","first-page":"69","article-title":"A method for the differential staining of Gram positive and Gram negative bacteria in tissue sections","author":"Brown JH BL","year":"1931","journal-title":"Bulletin of the John Hopkins"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v012a02"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.2c00330"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-020-00118-w"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2007.00094.x"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2006.00024.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1981.tb05620.x"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1990.tb19132.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25506"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2020.02.007"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00415-18"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.781022"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2019.02.005"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200948020-00002"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24949"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.11.009"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.25988","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T03:08:24Z","timestamp":1736132904000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.25988"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,9]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/jor.25988"],"URL":"https:\/\/doi.org\/10.1002\/jor.25988","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,9]]},"assertion":[{"value":"2024-06-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}