{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:40:44Z","timestamp":1792726844275,"version":"4.5.0"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["IK2 RX003928"],"award-info":[{"award-number":["IK2 RX003928"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I50 RX004845"],"award-info":[{"award-number":["I50 RX004845"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008982","name":"National Science Foundation of Sri Lanka","doi-asserted-by":"publisher","award":["DGE\u20102039655"],"award-info":[{"award-number":["DGE\u20102039655"]}],"id":[{"id":"10.13039\/501100008982","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytoskeleton"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Joint injuries are increasingly common and initiate a degenerative cascade in the cartilage extracellular matrix. Chondrocytes experience both intra\u2010 and extra\u2010cellular changes during the initial phases of this process, including inflammatory activation and morphological change, initiating a catabolic feedback cycle that progresses toward osteoarthritis (OA). However, the link between this early morphological spreading and susceptibility to future inflammatory events is unclear. Thus, the objective of this study was to explore the implications of cellular spreading on early inflammatory activation. First, we treated bovine cartilage explants with control or degenerative media for 2\u2009weeks and established early chondrocyte spreading and extracellular matrix loss around chondrocytes. Next, we either seeded chondrocytes on or encapsulated them within gelatin hydrogels of different stiffnesses to allow different degrees of spreading, followed by a short (2\u2009h) inflammatory stimulus to measure inflammatory activation (NF\u2010\u03baB). We found in 2D that stiffer substrates led to greater chondrocyte spreading and NF\u2010\u03baB nuclear localization; however, in 3D, this trend was reversed, with the greatest spreading and activation in cells in the softest hydrogels. Finally, we investigated how hyaluronic acid hydrogel incorporation into these environments could impact this spreading\u2010inflammtory activation relationship, showing that augmentation with HA reduced both facets. In conclusion, chondrocyte spreading, especially in 3D, is linked with reduced matrix stiffness, and this can make chondrocytes more susceptible to inflammation. Thus, future therapies should seek to address not only the inflammation in the joint but also to restore chondrocyte morphology and microenvironmental properties.<\/jats:p>","DOI":"10.1002\/cm.22011","type":"journal-article","created":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T12:57:53Z","timestamp":1741438673000},"page":"592-600","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Interplay Between Early Chondrocyte Spreading and Inflammatory Responsivity"],"prefix":"10.1002","volume":"82","author":[{"given":"Tristan Isaiah","family":"Pepper","sequence":"first","affiliation":[{"name":"Department of Veterans Affairs Joseph Maxwell Cleland Atlanta VA Medical Center  Decatur Georgia USA"},{"name":"Department of Orthopaedics Emory University School of Medicine  Atlanta Georgia USA"},{"name":"Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saitheja Adi","family":"Pucha","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs Joseph Maxwell Cleland Atlanta VA Medical Center  Decatur Georgia USA"},{"name":"Department of Orthopaedics Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Foster","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs Joseph Maxwell Cleland Atlanta VA Medical Center  Decatur Georgia USA"},{"name":"Department of Orthopaedics Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan Y.","family":"Liu","sequence":"additional","affiliation":[{"name":"Optics11 Life Inc.  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs Joseph Maxwell Cleland Atlanta VA Medical Center  Decatur Georgia USA"},{"name":"Morehouse School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4889-0818","authenticated-orcid":false,"given":"Jay Milan","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs Joseph Maxwell Cleland Atlanta VA Medical Center  Decatur Georgia USA"},{"name":"Department of Orthopaedics Emory University School of Medicine  Atlanta Georgia USA"},{"name":"Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2004.04.012"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24694"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23411"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/bioengineering10091013"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1063\u20104584(02)00369\u20102"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2020.05.005"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2017.03.001"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201511767"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2007.08.008"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2003.11.023"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2007.09.009"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926\u2010019\u20100837\u20106"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c09015"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2018.02.005"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.3352"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2016.05.019"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22063279"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201909802"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-200110001-00011"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201036500\u20102"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.25670"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/joa.12554"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2016.10.004"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202100315"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2019.01.061"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201003958\u20105"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11111806"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1101\/2023.12.08.570865"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v034a09"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2014.08.009"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/561459"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M509433200"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2021008"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2023144"}],"container-title":["Cytoskeleton"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cm.22011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T13:01:00Z","timestamp":1757595660000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cm.22011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,5]]},"references-count":34,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/cm.22011"],"URL":"https:\/\/doi.org\/10.1002\/cm.22011","archive":["Portico"],"relation":{},"ISSN":["1949-3584","1949-3592"],"issn-type":[{"value":"1949-3584","type":"print"},{"value":"1949-3592","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,5]]},"assertion":[{"value":"2024-09-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}