{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:10:42Z","timestamp":1792804242721,"version":"4.5.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:00:00Z","timestamp":1686528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Despite great efforts to develop microvascular bone chips in previous studies, current bone chips still lacked multi-component of human-derived cells close to human bone tissue. Bone microvascular endothelial cells (BMECs) were demonstrated to be closely related to the glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). Tumor necrosis factor-alpha (TNF-\u03b1) aptamer has been proved to bind to its receptor and block cascade activities.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Objective:<\/jats:bold>\n                    There are two main objectives in this study: 1) to establish a multi-component bone-on-a-chip within the microfluidic system\n                    <jats:italic>in vitro<\/jats:italic>\n                    , 2) to explore the therapeutic potential of TNF-\u03b1 aptamer on BMECs in the GC-induced ONFH model.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Histological features of clinical samples were analyzed before BMECs isolation. The functional bone-on-a-chip consists of the vascular channel, stromal channel and structure channel. GC-induced ONFH model was established based on the multi-component of human-derived cells. Truncation and dimerization were performed on a previously reported DNA aptamer (VR11). BMECs apoptosis, cytoskeleton and angiogenesis status in the ONFH model were observed by the TUNEL staining and confocal microscope.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    The multi-component of BMECs, human embryonic lung fibroblasts and hydroxyapatite were cultured within the microfluidic bone-on-a-chip. TNF-\u03b1 was found up-regulated in the necrotic regions of femoral heads in clinical samples and similar results were re-confirmed in the ONFH model established in the microfluidic platform by detecting cell metabolites. Molecular docking simulations indicated that the truncated TNF-\u03b1 aptamer could improve the aptamer-protein interactions. Further results from the TUNEL staining and confocal microscopy showed that the truncated aptamer could protect BMECs from apoptosis and alleviate GC-induced damages to cytoskeleton and vascularization.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    In summary, a microfluidic multi-component bone-on-a-chip was established with \u2018off-chip\u2019 analysis of cell metabolism. GC-induced ONFH model was achieved based on the platform. Our findings provided initial evidence on the possible potentials of TNF-\u03b1 aptamer as a new type of TNF-\u03b1 inhibitor for patients with ONFH.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2023.1183163","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:37:53Z","timestamp":1686530273000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Establishment of the multi-component bone-on-a-chip: to explore therapeutic potential of DNA aptamers on endothelial cells"],"prefix":"10.3389","volume":"11","author":[{"given":"Xiaoyu","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianhui","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyang","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1182\/blood-2011-04-325225","article-title":"Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey","volume":"119","author":"Aggarwal","year":"2012","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1038\/nri3834","article-title":"Regulation of tumour necrosis factor signalling: Live or let die","volume":"15","author":"Brenner","year":"2015","journal-title":"Nat. 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