{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T23:45:50Z","timestamp":1782431150821,"version":"3.54.5"},"reference-count":49,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Research in Veterinary Medicine Unit","award":["UID\/00772\/2025"],"award-info":[{"award-number":["UID\/00772\/2025"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["CARTILAGE"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This study investigated the dose-dependent cytotoxicity and immunomodulatory effects of intra-articular local anaesthetics (lidocaine, mepivacaine, levobupivacaine) and corticosteroids (dexamethasone, methylprednisolone, methylprednisolone acetate) on canine fibroblast-like synoviocytes (FLS)\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . We evaluated cell viability and the expression of IL-6 and MMP-9.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Canine FLS were exposed to increasing concentrations of intra-articular agents. Cell viability was determined via MTT assays. Immunomodulatory effects were assessed via ELISA for IL-6 and gelatin zymography for MMP-9 activity after TNF-\u03b1 stimulation with IC\n                      <jats:sub>50<\/jats:sub>\n                      concentrations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All agents exhibited dose-dependent cytotoxicity. Dexamethasone was most cytotoxic (IC\n                      <jats:sub>50<\/jats:sub>\n                      \u2248 3.4\u00d710\n                      <jats:sup>-4<\/jats:sup>\n                      mg\/mL) but selectively inhibited TNF-\u03b1-induced MMP-9 activity without affecting IL-6 or inducing cytotoxicity at its IC\n                      <jats:sub>50<\/jats:sub>\n                      . Mepivacaine significantly inhibited MMP-9 activity by 40% at 1 mg\/mL and uniquely induced IL-6 in unstimulated cells. Lidocaine, methylprednisolone, and methylprednisolone acetate suppressed TNF-\u03b1-induced IL-6 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Commonly used intra-articular agents induce dose-dependent cytotoxic effects on canine FLS at clinically relevant concentrations. This study provides the first evidence of species-specific responses for mepivacaine, levobupivacaine, and dexamethasone in canine FLS, highlighting mediator-specific and concentration-dependent effects crucial for optimizing intra-articular therapies in veterinary and translational medicine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/19476035261459650","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T18:57:21Z","timestamp":1782154641000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["In Vitro Cytotoxicity and Inflammatory Response of Local Anaesthetics and Corticosteroids in Canine Fibroblast-Like Synoviocytes"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5172-7806","authenticated-orcid":false,"given":"Catarina","family":"Sousa","sequence":"first","affiliation":[{"name":"Lus\u00f3fona University \u2013 Lisbon University Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Lima","sequence":"additional","affiliation":[{"name":"Lus\u00f3fona University \u2013 Lisbon University Center"},{"name":"IPLUSO \u2013 Polytechnic Institute of Lusofonia"},{"name":"Lus\u00f3fona University \u2013 Lisbon University Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Belas","sequence":"additional","affiliation":[{"name":"Lus\u00f3fona University \u2013 Lisbon University Center"},{"name":"IPLUSO \u2013 Polytechnic Institute of Lusofonia"},{"name":"Lus\u00f3fona University \u2013 Lisbon University Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f3nia","family":"Campos","sequence":"additional","affiliation":[{"name":"Lus\u00f3fona University \u2013 Lisbon University Center"},{"name":"IPLUSO \u2013 Polytechnic Institute of Lusofonia"},{"name":"Lus\u00f3fona University \u2013 Lisbon University Center"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(23)00163-7"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.2460\/javma.229.5.690"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12917-020-02647-2"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1385006"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ani13071223"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231911817"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-019-0202-1"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1297361"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/2040622312454157"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1177\/1076029621995569"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/1947603515594453"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1292\/jvms.22-0563"},{"key":"e_1_3_4_14_2","first-page":"107","article-title":"In vivo toxicity of local anaesthetics and corticosteroids on supraspinatus tenocyte cell viability and metabolism","volume":"38","author":"Nuelle CW","year":"2018","unstructured":"Nuelle CW, Cook CR, Stoker AM, Cook JL, Sherman SL. 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