{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T03:12:58Z","timestamp":1779333178392,"version":"3.51.4"},"reference-count":90,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P30 GM131959"],"award-info":[{"award-number":["P30 GM131959"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20 GM121342"],"award-info":[{"award-number":["P20 GM121342"]}],"id":[{"id":"10.13039\/100000002","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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Dysregulation of synovial homeostasis has been implicated in the pathophysiology of osteoarthritis (OA), but the effects that cigarette smoking has on OA\u2010affected synovium have yet to be studied. To further the knowledge on how cigarette smoke alters OA progression, we investigated the direct effects of cigarette smoke extract (CSE) on synovial explants and the indirect impact this has on cartilage explant degradation in an in vitro model of OA\u2010like inflammation. Porcine synovium explants were cultured under control (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098), OA only (IL\u20101\u03b2 and TNF\u2010\u03b1,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098), and CSE\u2009+\u2009OA (10% CSE, IL\u20101\u03b2 and TNF\u2010\u03b1,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098) conditions. The resulting changes in viability\/metabolic activity, reactive oxygen species (ROS) production, inflammatory cytokine and matrix metalloprotease profile, and macrophage polarization were evaluated. Using an indirect co\u2010culture model, cartilage explants (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098\/group) were cultured in synovium conditioned media (SCM) under the aforementioned conditions to evaluate changes in viability\/metabolic activity, ROS, and extracellular matrix (ECM) integrity. CSE\u2009+\u2009OA treated synovium had increased production of ROS, IL\u20108, MMP\u20102, and MMP\u20108 compared to OA only treated synovium. In response, cartilage explants under CSE\u2009+\u2009OA SCM had more chondrocytes stained positively for ROS, with accelerated losses in GAGs and ECM integrity compared to those exposed to OA only SCM. CSE may accelerate OA progression by altering the inflammatory secretory profile of synovium and contributing to increased oxidative stress and the pathological crosstalk between synovium and cartilage.\n                  <\/jats:p>","DOI":"10.1002\/jor.70184","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T04:17:42Z","timestamp":1774930662000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cigarette Smoke Extract Alters the Inflammatory Secretome of Osteoarthritis\u2010Affected Synovium Increasing Joint Tissue Oxidative Stress in an Indirect Co\u2010Culture Model"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2072-6840","authenticated-orcid":false,"given":"Emily Sawvell","family":"DiNicola","sequence":"first","affiliation":[{"name":"The Laboratory of Orthopaedic Tissue Regeneration &amp; Orthobiologics, Department of Bioengineering Clemson University Clemson South Carolina USA"},{"name":"Frank H. Stelling and C. Dayton Riddle Orthopaedic Education and Research Laboratory Clemson University Biomedical Engineering Innovation Campus Greenville South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea Vera","family":"Martinez","sequence":"additional","affiliation":[{"name":"The Laboratory of Orthopaedic Tissue Regeneration &amp; Orthobiologics, Department of Bioengineering Clemson University Clemson South Carolina USA"},{"name":"Frank H. Stelling and C. Dayton Riddle Orthopaedic Education and Research Laboratory Clemson University Biomedical Engineering Innovation Campus Greenville South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian C.","family":"Burnikel","sequence":"additional","affiliation":[{"name":"Prisma Health Steadman Hawkins Clinic of the Carolinas\u2014Patewood Greenville South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8719-6672","authenticated-orcid":false,"given":"Jeremy J.","family":"Mercuri","sequence":"additional","affiliation":[{"name":"The Laboratory of Orthopaedic Tissue Regeneration &amp; Orthobiologics, Department of Bioengineering Clemson University Clemson South Carolina USA"},{"name":"Frank H. Stelling and C. Dayton Riddle Orthopaedic Education and Research Laboratory Clemson University Biomedical Engineering Innovation Campus Greenville South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2013.03.018"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(23)00163-7"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2020.100587"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1302\/2046-3758.1112.BJR-2022-0215.R1"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmu116"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22179208"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9030594"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202001071R"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1164137"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1269724"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/joa.12820"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12242850"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-023-00301-9"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.43143"},{"key":"e_1_2_9_16_1","unstructured":"National Center for Chronic Disease Prevention and Health Promotion (US) Office on Smoking and Health. The Health Consequences of Smoking\u201450 Years of Progress: A Report of the Surgeon General. [Internet].2014. Report https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK179276\/."},{"key":"e_1_2_9_17_1","unstructured":"P. V.MarquezWorld Bank Blogs. 2021. An ominous fact on World No Tobacco Day \u2013 2021: Smoking kills more people than COVID\u201019."},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/tobaccocontrol-2021-056535"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2025.40.e331"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-023-06953-2"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2014.11.022"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/15353702231199072"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21051901"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-010-1644-6"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.25828"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12091732"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s42269-024-01174-6"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2021.108365"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11061153"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.1001212"},{"key":"e_1_2_9_31_1","unstructured":"Ordinary one\u2010way ANOVA followed by Tukey's multiple comparisons test was performed using GraphPad Prism version 10.6.1 for MacOS X GraphPad Software www.graphpad.com."},{"key":"e_1_2_9_32_1","unstructured":"Repeated\u2010measures mixed\u2010effects analysis with multiple comparisons was performed using GraphPad Prism version 10.6.1 for MacOS X GraphPad Software www.graphpad.com."},{"key":"e_1_2_9_33_1","unstructured":"Outliers were detected using the ROUT method (Q = 5%) implemented in GraphPad Prism version 10.6.1 for MacOS X GraphPad Software www.graphpad.com."},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2012.0107"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2007.0081"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-014-1139-0"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.27.407"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874312901105010100"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-022-00749-9"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-070202857-1.50008-1"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101249"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0230719"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-021-00697-6"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.12431"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0214709"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01150-z"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2012.02.012"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.720477"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.159"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.2610"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X10378373"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.678757"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2024.12490"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.13228"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2016.69"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2017.49"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40504"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2013.08.018"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1010337"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2023.10.032"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.09.025"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.5114\/pja.2022.116285"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20220525"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12956"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13888-x"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-024-00318-8"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-213450"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.155.5.9154890"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-6-74"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0068199"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-018-0114-1"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00046.2012"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.196"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23471"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.3390\/immuno3030017"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9080739"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jobcr.2015.08.004"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbiosy.2024.100090"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms151222279"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ken259"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-eular.5405"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-60305-x"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9020475"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370219896545"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.15386\/mpr-1422"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.056697"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.3109\/03009742.2011.599073"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-67730-y"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2015.02.168"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11237125"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.625497"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.70184","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jor.70184","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.70184","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T02:33:43Z","timestamp":1779330823000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.70184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,30]]},"references-count":90,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/jor.70184"],"URL":"https:\/\/doi.org\/10.1002\/jor.70184","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,30]]},"assertion":[{"value":"2025-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70184"}}