{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T08:40:15Z","timestamp":1793781615512,"version":"4.6.1"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100008542","name":"Arthroscopy Association of North America","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007710","name":"University of Connecticut","doi-asserted-by":"publisher","award":["07-224-02"],"award-info":[{"award-number":["07-224-02"]}],"id":[{"id":"10.13039\/100007710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["arthroscopyjournal.org","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Arthroscopy"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To quantify cellular senescence in supraspinatus tendon and subacromial bursa of humans with rotator cuff tears and to investigate the in\u00a0vitro efficacy of the senolytic dasatinib\u00a0+ quercetin (D+Q) to eliminate senescent cells and alter tenogenic differentiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Tissue was harvested from 41 patients (mean age, 62 years) undergoing arthroscopic rotator cuff repairs. In part 1 (n\u00a0= 35), senescence was quantified using immunohistochemistry and gene expression for senescent cell markers (p16 and p21) and the senescence\u2010associated secretory phenotype (SASP) (interleukin [IL] 6, IL\u20108, matrix metalloproteinase [MMP] 3, monocyte chemoattractant protein [MCP] 1). Senescence was compared between patients &lt;60 and \u226560 years old. In part 2 (n\u00a0= 6) , an in\u00a0vitro model of rotator cuff tears was treated with D+Q or control. D+Q, a chemotherapeutic and plant flavanol, respectively, kill senescent cells. Gene expression analysis assessed the ability of D+Q to kill senescent cells and alter markers of tenogenic differentiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Part 1 revealed an age\u2010dependent significant increase in the relative expression of p21, IL\u20106, and IL\u20108 in tendon and p21, p16, IL\u20106, IL\u20108, and MMP\u20103 in bursa (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; .05). A significant increase was seen in immunohistochemical staining of bursa p21 (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.028). In part 2, D+Q significantly decreased expression of p21, IL\u20106, and IL\u20108 in tendon and p21 and IL\u20108 in bursa (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a0.05). Enzyme\u2010linked immunosorbent assay analysis showed decreased release of the SASP (IL\u20106, MMP\u20103, MCP\u20101;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.002,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0= .024,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt; .001, respectively). Tendon (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0= .022) and bursa (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0= .027) treated with D+Q increased the expression of COL1A1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>While there was an age\u2010dependent increase in markers of cellular senescence, this relationship was not consistently seen across all markers and tissues. Dasatinib\u00a0+ quercetin had moderate efficacy in decreasing senescence in these tissues and increasing COL1A1 expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance<\/jats:title>\n                    <jats:p>This study reveals that cellular senescence may be a therapeutic target to alter the biological aging of rotator cuffs and identifies D+Q as a potential therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.arthro.2023.05.036","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T15:11:01Z","timestamp":1687619461000},"page":"34-44","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":22,"title":["Human Rotator Cuff Tears Reveal an Age\u2010Dependent Increase in Markers of Cellular Senescence and Selective Removal of Senescent Cells With Dasatinib\u00a0+ Quercetin Increases Genetic Expression of COL1A1 In\u00a0Vitro"],"prefix":"10.1002","volume":"40","author":[{"given":"Benjamin C.","family":"Hawthorne","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery University of Connecticut Farmington Connecticut U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian J.","family":"Wellington","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Connecticut Farmington Connecticut U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua T.","family":"Sabitsky","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Connecticut Farmington Connecticut U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle V.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Connecticut Farmington Connecticut U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen P.","family":"Karsmarski","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Connecticut Farmington Connecticut U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohin O.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Connecticut Farmington Connecticut U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"LeVasseur","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Connecticut Farmington Connecticut U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Mancini","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Connecticut Farmington Connecticut 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