{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T10:42:14Z","timestamp":1792579334259,"version":"4.5.0"},"reference-count":50,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Washinton University"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Am J Sports Med"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The high incidence of posttraumatic osteoarthritis after anterior cruciate ligament (ACL) injury and reconstruction suggests that biological mechanisms beyond joint instability contribute to disease progression. After injury, ACL-resident cells are exposed to inflammatory mediators within the joint and may influence the local inflammatory microenvironment; however, their global transcriptomic responses to inflammatory stimuli remain underexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis:<\/jats:title>\n                    <jats:p>Interleukin-1 beta (IL-1\u03b2) induces inflammatory transcriptomic responses in ACL remnant\u2013derived (ACLr) fibroblasts, and transforming growth factor beta 1 (TGF-\u03b21) attenuates these responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design:<\/jats:title>\n                    <jats:p>Descriptive laboratory study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Primary ACLr fibroblasts were isolated from ACL remnants (n = 10) collected at the time of knee surgery. Near-confluent cultures were treated with IL-1\u03b2 (10 ng\/mL) for 24 hours to model an inflammatory joint environment. Genome-wide transcriptional changes were assessed by RNA sequencing using an Illumina NovaSeq-6000, with selected targets confirmed by microfluidic digital polymerase chain reaction (PCR). To evaluate the effects of TGF-\u03b21, ACLr fibroblasts pretreated with IL-1\u03b2 were exposed to TGF-\u03b21 (10 ng\/mL) for 48 hours, and chemokine transcript levels were assessed using digital PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      IL-1\u03b2 induced broad inflammatory transcriptional responses characterized by upregulation of chemokines (\n                      <jats:italic toggle=\"yes\">CXCL6<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">CXCL8<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">CXCL5<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">CCL20<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">CXCL1<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">CXCL3<\/jats:italic>\n                      ), cytokines (\n                      <jats:italic toggle=\"yes\">IL33<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">IL1B<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">IL6<\/jats:italic>\n                      ), and matrix-degrading enzymes (\n                      <jats:italic toggle=\"yes\">MMP3<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">MMP12<\/jats:italic>\n                      ), while suppressing extracellular matrix-associated genes (\n                      <jats:italic toggle=\"yes\">KRT14<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">COL21A1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">POSTN<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">COL1A1<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">COL6A3<\/jats:italic>\n                      ). Functional enrichment analysis demonstrated activation of immune and inflammatory responses, cytokine and chemokine signaling, and cell activation. TGF-\u03b21 reduced the expression of all assessed IL-1\u03b2\u2013induced chemokines, with reduction of up to 50%, with statistically significant suppression observed for 13 of the 16 chemokines. Concomitantly, TGF-\u03b21 treatment reduced expression of\n                      <jats:italic toggle=\"yes\">CEBPB<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">NFKBIA<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">NFKBIZ<\/jats:italic>\n                      , transcripts implicated in inflammatory gene regulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>ACLr fibroblasts mounted a robust inflammatory transcriptomic response to IL-1\u03b2, characterized by marked induction of chemokines and inflammatory pathways. TGF-\u03b21 attenuated many of these responses, supporting its role as a regulator of inflammatory signaling in ACL-resident cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance:<\/jats:title>\n                    <jats:p>ACL-resident cells respond to injury and may contribute to the post-injury inflammatory microenvironment. Therapeutic modulation of inflammatory signaling in these cells could represent a strategy to mitigate early molecular events associated with post-traumatic osteoarthritis following ACL tear.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03635465261470174","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:17:27Z","timestamp":1786969047000},"page":"3005-3018","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["IL-1\u03b2\u2013Induced Inflammatory Transcriptome and TGF-\u03b21 Attenuation of Chemokine Expression in ACL Remnant Fibroblasts"],"prefix":"10.1177","volume":"54","author":[{"given":"Lei","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Washington University, St. Louis, Missouri, 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