{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T08:06:07Z","timestamp":1770537967352,"version":"3.49.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32271381"],"award-info":[{"award-number":["32271381"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cell apoptosis or necrosis, extracellular matrix loss, and excessive inflammation may induce tendon graft degeneration. The impairment in the regeneration capability of nerve fibers and blood vessels may be the critical cause. Calcitonin gene\u2010related peptide (CGRP), exhibiting a short half\u2010life, favors cell proliferation, nerve fiber regeneration and angiogenesis. We aimed to investigate the effects of CGRP receptor\u2010mediated signaling on tendon graft integrity and study if the modulation pathways are ascribed to cell proliferation, nerve fiber and blood vessel regeneration. A total of three groups in mice with ACL reconstruction were established: the control group (PBS treatment), the adenovirus vectors expressing CGRP receptor (CALCRL) treated group (Adv\u2010<jats:italic>Calcrl<\/jats:italic> treatment), and the adenovirus vectors carrying shRNA targeting <jats:italic>Calcrl<\/jats:italic> treated group (Adv\u2010sh<jats:italic>Calcrl<\/jats:italic> treatment). The histological assessment indicated the Adv\u2010<jats:italic>Calcrl<\/jats:italic> treatment was favored while the Adv\u2010sh<jats:italic>Calcrl<\/jats:italic> significantly impaired tendon graft integrity. TUNEL staining revealed a significant decreased number of apoptotic cells in the Adv\u2010<jats:italic>Calcrl<\/jats:italic> group relative to the control group and the adv\u2010sh<jats:italic>Calcrl<\/jats:italic> group. Compared to the control group and the Adv\u2010sh<jats:italic>Calcrl<\/jats:italic> group, the Adv\u2010<jats:italic>Calcrl<\/jats:italic> group showed significantly enhanced proliferation of nestin positive cells. Of note, the Adv\u2010<jats:italic>Calcrl<\/jats:italic> treatment significantly increased EMCN expression at the tendon graft relative to the control and the Adv\u2010sh<jats:italic>Calcrl<\/jats:italic> groups, which may be ascribed to attenuation of the Hippo signaling pathway. Importantly, the Adv\u2010<jats:italic>Calcrl<\/jats:italic> treatment significantly increased sensory nerve fibers and also PIEZO2 levels. Our results demonstrate the activation of CGRP receptor\u2010mediated signaling attenuated tendon graft degeneration, which was ascribed to enhanced proliferation of Nestin positive cells, angiogenesis, and nerve fiber outgrowth.<\/jats:p>","DOI":"10.1002\/jor.25978","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T07:22:43Z","timestamp":1727248963000},"page":"37-45","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Overexpression of CGRP receptor attenuates tendon graft degeneration in anterior cruciate ligament reconstruction"],"prefix":"10.1002","volume":"43","author":[{"given":"Xibang","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering Shenzhen Campus of Sun Yat\u2010sen University Shenzhen 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