{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:05:41Z","timestamp":1790877941600,"version":"4.1.0"},"reference-count":49,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:00:00Z","timestamp":1611792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"national institutes of health","doi-asserted-by":"publisher","award":["R01-AR057836 and R01-AR072623"],"award-info":[{"award-number":["R01-AR057836 and R01-AR072623"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Am J Sports Med"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>More than 450,000 rotator cuff repairs are performed annually, yet healing of tendon to bone often fails. This failure is rooted in the fibrovascular healing response, which does not regenerate the native attachment site. Better healing outcomes may be achieved by targeting inflammation during the early period after repair. Rather than broad inhibition of inflammation, which may impair healing, the current study utilized a molecularly targeted approach to suppress IKK\u03b2, shutting down only the inflammatory arm of the nuclear factor \u03baB (NF-\u03baB) signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>To evaluate the therapeutic potential of IKK\u03b2 inhibition in a clinically relevant model of rat rotator cuff repair.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design:<\/jats:title>\n                    <jats:p>Controlled laboratory study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>After validating the efficacy of the IKK\u03b2 inhibitor in vitro, it was administered orally once a day for 7 days after surgery in a rat rotator cuff repair model. The effect of treatment on reducing inflammation and improving repair quality was evaluated after 3 days and 2, 4, and 8 weeks of healing, using gene expression, biomechanics, bone morphometry, and histology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Inhibition of IKK\u03b2 attenuated cytokine and chemokine production in vitro, demonstrating the potential for this inhibitor to reduce inflammation in vivo. Oral treatment with IKK\u03b2 inhibitor reduced NF-\u03baB target gene expression by up to 80% compared with a nontreated group at day 3, with a subset of these genes suppressed through 14 days. Furthermore, the IKK\u03b2 inhibitor led to enhanced tenogenesis and extracellular matrix production, as demonstrated by gene expression and histological analyses. At 4 weeks, inhibitor treatment led to increased toughness, no effects on failure load and strength, and decreases in stiffness and modulus when compared with vehicle control. At 8 weeks, IKK\u03b2 inhibitor treatment led to increased toughness, failure load, and strength compared with control animals. IKK\u03b2 inhibitor treatment prevented the bone loss near the tendon attachment that occurred in repairs in control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Pharmacological inhibition of IKK\u03b2 successfully suppressed excessive inflammation and enhanced tendon-to-bone healing after rotator cuff repair in a rat model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance:<\/jats:title>\n                    <jats:p>The NF-\u03baB pathway is a promising target for enhancing outcomes after rotator cuff repair.<\/jats:p>\n                  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