{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:56:42Z","timestamp":1786539402204,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T00:00:00Z","timestamp":1699228800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["2011042"],"award-info":[{"award-number":["2011042"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The intracellular infection of osteocytes represents a clinically important aspect of osteomyelitis. However, few human osteocyte in\u00a0vitro models exist and the differentiation of immature osteoblasts to an osteocyte stage typically takes at least 4\u2010weeks of culture, making the study of this process challenging and time consuming. The osteosarcoma cell line Saos\u20102 has proved to be a useful model of human osteoblast to mature osteocyte differentiation. Culture under osteogenic conditions in a standard normoxic (21% O<jats:sub>2<\/jats:sub>) atmosphere results in reproducible mineralization and acquisition of mature osteocyte markers over the expected 28\u201335\u2009day culture period. In order to expedite experimental assays, we tested whether reducing available oxygen to mimic concentrations experienced by osteocytes in\u00a0vivo would increase the rate of differentiation. Cells cultured under 1% O<jats:sub>2<\/jats:sub> exhibited maximal mineral deposition by 14\u2009days. Early (<jats:italic>COLA1<\/jats:italic>, <jats:italic>MEPE<\/jats:italic>) and mature (<jats:italic>PHEX<\/jats:italic>, <jats:italic>DMP1<\/jats:italic>, <jats:italic>GJA1<\/jats:italic>, <jats:italic>SOST<\/jats:italic>) osteocyte markers were upregulated earlier under hypoxia compared to normoxia. Cells differentiated under 1% O<jats:sub>2<\/jats:sub> for 14\u2009days displayed a similar ability to internalize <jats:italic>Staphylococcus aureus<\/jats:italic> as day 28 cells grown under normoxic conditions. Thus, low oxygen accelerates Saos\u20102 osteocyte differentiation, resulting in a useful human osteocyte\u2010like cell model within 14\u2009days.<\/jats:p>","DOI":"10.14814\/phy2.15851","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T09:59:09Z","timestamp":1699264749000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Saos\u20102 cells cultured under hypoxia rapidly differentiate to an osteocyte\u2010like stage and support intracellular infection by <i>Staphylococcus aureus<\/i>"],"prefix":"10.14814","volume":"11","author":[{"given":"Anja R.","family":"Zelmer","sequence":"first","affiliation":[{"name":"Biomedical Orthopaedic Research Group, Centre for Orthopaedic &amp; Trauma Research, Faculty of Health and Medical Sciences University of Adelaide  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolandi","family":"Starczak","sequence":"additional","affiliation":[{"name":"Biomedical Orthopaedic Research Group, Centre for Orthopaedic &amp; Trauma Research, Faculty of Health and Medical Sciences University of Adelaide  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucian B.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Centre for Orthopaedic &amp; Trauma Research, Faculty of Health and Medical Sciences University of Adelaide  Adelaide South Australia Australia"},{"name":"Department of Orthopaedics and Trauma Royal Adelaide Hospital  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Richter","sequence":"additional","affiliation":[{"name":"Richter Lab, Department of Surgery Basil Hetzel Institute for Translational Health Research, University of Adelaide  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongqing","family":"Yang","sequence":"additional","affiliation":[{"name":"Biomedical Orthopaedic Research Group, Centre for Orthopaedic &amp; Trauma Research, Faculty of Health and Medical Sciences University of Adelaide  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3123-9861","authenticated-orcid":false,"given":"Gerald J.","family":"Atkins","sequence":"additional","affiliation":[{"name":"Biomedical Orthopaedic Research Group, Centre for Orthopaedic &amp; Trauma Research, Faculty of Health and Medical Sciences University of Adelaide  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12070960"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2007.02.024"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-008-0728-6"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftx005"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.110.070508"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.320"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.090517"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0065940"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.CC.17.00154"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.405456"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22559"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2016.07.047"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.781022"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-007-0765-9"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2019.00288"},{"key":"e_1_2_10_17_1","first-page":"43","volume-title":"Osteoimmunology: Interactions of the Immune and Skeletal Systems II","author":"Komori T.","year":"2010"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20071694"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2012.07.005"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2016.10.005"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.07.007"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2016.01.016"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v042a19"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2009.06.010"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-4221fje"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2016.02.003"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-014-9879-y"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7TB03251J"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.276683"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-50236-7"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2001.16.11.2017"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23063233"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2006.02.007"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31581"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.06.013"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2015.06.021"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2015.06.005"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00415-18"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.08.016"}],"container-title":["Physiological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.15851","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T04:04:00Z","timestamp":1705032240000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.14814\/phy2.15851"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11]]},"references-count":38,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.14814\/phy2.15851"],"URL":"https:\/\/doi.org\/10.14814\/phy2.15851","archive":["Portico"],"relation":{},"ISSN":["2051-817X","2051-817X"],"issn-type":[{"value":"2051-817X","type":"print"},{"value":"2051-817X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11]]},"assertion":[{"value":"2023-06-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e15851"}}