{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:06:47Z","timestamp":1787508407990,"version":"build-2736575974"},"reference-count":49,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2023,6,17]],"date-time":"2023-06-17T00:00:00Z","timestamp":1686960000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100001460","name":"American Orthopaedic Foot and Ankle Society","doi-asserted-by":"publisher","award":["AOFAS 2021-21838-S"],"award-info":[{"award-number":["AOFAS 2021-21838-S"]}],"id":[{"id":"10.13039\/100001460","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Foot Ankle Int."],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The first stage of fracture healing consists of hematoma formation with recruitment of proinflammatory cytokines and matrix metalloproteinases. Unfortunately, when there is an intra-articular fracture, these inflammatory mediators are not retained at the fracture site, but instead, envelop the healthy cartilage of the entire joint via the synovial fluid fracture hematoma (SFFH). These inflammatory cytokines and matrix metalloproteinases are known factors in the progression of osteoarthritis and rheumatoid arthritis. Despite the known inflammatory contents of the SFFH, little research has been done on the effects of the SFFH on healthy cartilage with regard to cell death and alteration in gene expression that could lead to posttraumatic osteoarthritis (PTOA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>SFFH was collected from 12 patients with intraarticular ankle fracture at the time of surgery. Separately, C20A4 immortalized human chondrocytes were 3-dimensionally cultured to create scaffold-free cartilage tissue analogs (CTAs) to simulate healthy cartilage. Experimental CTAs (n\u2009=\u200912) were exposed to 100% SFFH for 3\u2009days, washed, and transferred to complete media for 3\u2009days. Control CTAs (n\u2009=\u200912) were simultaneously cultured in complete medium without exposure to SFFH. Subsequently, CTAs were harvested and underwent biochemical, histological, and gene expression analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Exposure of CTAs to ankle SFFH for 3\u2009days significantly decreased chondrocyte viability by 34% (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.027). Gene expression of both\n                      <jats:italic toggle=\"yes\">COL2A1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">SOX9<\/jats:italic>\n                      were significantly decreased after exposure to SFFH (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.012 and\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.0013 respectively), while there was no difference in\n                      <jats:italic toggle=\"yes\">COL1A1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">RUNX2<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">MMP13<\/jats:italic>\n                      gene expression. Quantitative analysis of Picrosirius red staining demonstrated increased collagen I deposition with poor ultrastructural organization in SFFH-exposed CTAs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Exposure of an organoid model of healthy cartilage tissue to SFFH after intraarticular ankle fracture resulted in decreased chondrocyte viability, decreased expression of genes regulating normal chondrocyte phenotype, and altered matrix ultrastructure indicating differentiation toward an osteoarthritis phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance:<\/jats:title>\n                    <jats:p>The majority of ankle fracture open reduction and internal fixation does not occur immediately after fracture. In fact, typically these fractures are treated several days to weeks later in order to let the swelling subside. This means that the healthy innocent bystander cartilage not involved in the fracture is exposed to SFFH during this time. In this study, the SFFH caused decreased chondrocyte viability and specific altered gene expression that might have the potential to induce osteoarthritis. These data suggest that early intervention after intraarticular ankle fracture could possibly mitigate progression toward PTOA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10711007231178829","type":"journal-article","created":{"date-parts":[[2023,6,17]],"date-time":"2023-06-17T07:33:50Z","timestamp":1686987230000},"page":"922-930","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Exposure of Tissue-Engineered Cartilage Analogs to Synovial Fluid Hematoma After Ankle Fracture Is Associated With Chondrocyte Death and Altered Cartilage Maintenance Gene Expression"],"prefix":"10.1177","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4866-125X","authenticated-orcid":false,"given":"Nicholas B.","family":"Allen","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7470-0067","authenticated-orcid":false,"given":"Alexandra Hunter","family":"Aitchison","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0303-5949","authenticated-orcid":false,"given":"Kian","family":"Bagheri","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Guardino","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5184-5762","authenticated-orcid":false,"given":"Bijan","family":"Abar","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA"},{"name":"Department of Mechanical Engineering and Material Science, Duke University, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel B.","family":"Adams","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,6,17]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/1071100717690427"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/1071100714550652"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/1071100717728234"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/1071100715611176"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/S41413-018-0021-Z"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(03)00049-0"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/10711007211046952\/FORMAT\/EPUB"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/JOR.21359"},{"key":"e_1_3_2_10_2","first-page":"1","article-title":"The pathomechanical etiology of post-traumatic osteoarthritis following intraarticular fractures","volume":"31","author":"Anderson DD","year":"2011","unstructured":"Anderson DD, Marsh JL, Brown TD. 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