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Unexpectedly, the tendons\u2019 collagen molecules were not mechanically unfolded by running but denatured through proteolysis during physiological post-run remodeling. We further revealed that running induces inflammatory gene expressions in Achilles tendons and that long-term running causes prolonged, elevated collagen degradation, leading to the accumulation of denatured collagen and tendinopathy development. For applications, we demonstrated magnetic resonance imaging of collagenase-induced Achilles tendon injury in vivo using a denatured collagen targeting contrast agent. Our findings may help close the knowledge gaps in the mechanobiology and pathogenesis of Achilles tendinopathy and initiate new strategies for its imaging-based diagnosis.<\/jats:p>","DOI":"10.1126\/sciadv.ado2015","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T17:58:33Z","timestamp":1727891913000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":25,"title":["Collagen denaturation in post-run Achilles tendons and Achilles tendinopathy: In vivo mechanophysiology and magnetic resonance imaging"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7094-6753","authenticated-orcid":true,"given":"Yijie","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Radiology, Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2468-7658","authenticated-orcid":true,"given":"Dantian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Radiology, Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5295-9432","authenticated-orcid":true,"given":"Jingyue","family":"Wei","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Engineering Research Center of Molecular Imaging, Biobank, Department of Information Technology and Data Center, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong 519000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5855-5779","authenticated-orcid":true,"given":"Lei","family":"Qian","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, National Virtual &amp; 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