{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:26:47Z","timestamp":1791556007388,"version":"4.3.4"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":40,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR001998"],"award-info":[{"award-number":["UL1TR001998"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR072061"],"award-info":[{"award-number":["AR072061"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med"],"DOI":"10.1186\/s12916-026-04818-8","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T02:34:07Z","timestamp":1774492447000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Multi-omics analysis reveals sex-specific etiology of human muscle weakness following musculoskeletal injury"],"prefix":"10.1186","volume":"24","author":[{"given":"Alexander R.","family":"Keeble","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison M.","family":"Owen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas T.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gonzalez-Velez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille R.","family":"Brightwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas E.","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip A.","family":"Kern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin E.","family":"Conley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin V.","family":"Stone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren L.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Noehren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher S.","family":"Fry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"issue":"11","key":"4818_CR1","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1302\/2046-3758.1111.BJR-2022-0181.R1","volume":"11","author":"V Ponkilainen","year":"2022","unstructured":"Ponkilainen V, Kuitunen I, Liukkonen R, Vaajala M, Reito A, Uimonen M. The incidence of musculoskeletal injuries: a systematic review and meta-analysis. Bone Joint Res. 2022;11(11):814\u201325.","journal-title":"Bone Joint Res"},{"issue":"6","key":"4818_CR2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2022-062183","volume":"12","author":"S Liu","year":"2022","unstructured":"Liu S, Wang B, Fan S, Wang Y, Zhan Y, Ye D. Global burden of musculoskeletal disorders and attributable factors in 204 countries and territories: a secondary analysis of the Global Burden of Disease 2019 study. BMJ Open. 2022;12(6):e062183.","journal-title":"BMJ Open"},{"issue":"15","key":"4818_CR3","doi-asserted-by":"publisher","first-page":"E973","DOI":"10.1097\/BRS.0000000000003576","volume":"45","author":"B Shahidi","year":"2020","unstructured":"Shahidi B, Ward SR. Letter to editor and response. Spine (Phila Pa 1976). 2020;45(15):E973\u20134.","journal-title":"Spine (Phila Pa 1976)"},{"issue":"6","key":"4818_CR4","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1097\/JSM.0000000000000290","volume":"26","author":"J Agel","year":"2016","unstructured":"Agel J, Rockwood T, Klossner D. Collegiate ACL injury rates across 15 sports: National Collegiate Athletic Association injury surveillance system data update (2004-2005 through 2012-2013). Clin J Sport Med. 2016;26(6):518\u201323.","journal-title":"Clin J Sport Med"},{"issue":"7","key":"4818_CR5","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1177\/0363546518773757","volume":"46","author":"KE Webster","year":"2018","unstructured":"Webster KE, Nagelli CV, Hewett TE, Feller JA. Factors associated with psychological readiness to return to sport after anterior cruciate ligament reconstruction surgery. Am J Sports Med. 2018;46(7):1545\u201350.","journal-title":"Am J Sports Med"},{"key":"4818_CR6","doi-asserted-by":"publisher","DOI":"10.1177\/19417381241230612","author":"MK Owen","year":"2024","unstructured":"Owen MK, Casadonte KR, Thomas NT, Latham CM, Brightwell CR, Thompson KL, et al. Sex differences in quadriceps atrophy after anterior cruciate ligament tear. Sports Health. 2024. https:\/\/doi.org\/10.1177\/19417381241230612.","journal-title":"Sports Health"},{"key":"4818_CR7","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.ptsp.2019.04.008","volume":"38","author":"C Kuenze","year":"2019","unstructured":"Kuenze C, Lisee C, Birchmeier T, Triplett A, Wilcox L, Schorfhaar A, et al. Sex differences in quadriceps rate of torque development within 1\u202fyear of ACL reconstruction. Phys Ther Sport. 2019;38:36\u201343.","journal-title":"Phys Ther Sport"},{"issue":"21","key":"4818_CR8","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1136\/bjsports-2013-093398","volume":"48","author":"CL Ardern","year":"2014","unstructured":"Ardern CL, Taylor NF, Feller JA, Webster KE. Fifty-five per cent return to competitive sport following anterior cruciate ligament reconstruction surgery: an updated systematic review and meta-analysis including aspects of physical functioning and contextual factors. Br J Sports Med. 2014;48(21):1543\u201352.","journal-title":"Br J Sports Med"},{"issue":"6","key":"4818_CR9","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1177\/03635465000280060301","volume":"28","author":"FK Noojin","year":"2000","unstructured":"Noojin FK, Barrett GR, Hartzog CW, Nash CR. Clinical comparison of intraarticular anterior cruciate ligament reconstruction using autogenous semitendinosus and gracilis tendons in men versus women. Am J Sports Med. 2000;28(6):783\u20139.","journal-title":"Am J Sports Med"},{"issue":"12","key":"4818_CR10","doi-asserted-by":"publisher","first-page":"3847","DOI":"10.1589\/jpts.27.3847","volume":"27","author":"DK Kim","year":"2015","unstructured":"Kim DK, Park WH. Sex differences in knee strength deficit 1\u2005year after anterior cruciate ligament reconstruction. J Phys Ther Sci. 2015;27(12):3847\u20139.","journal-title":"J Phys Ther Sci"},{"key":"4818_CR11","doi-asserted-by":"crossref","unstructured":"Fry CS, Johnson DL, Ireland ML, Noehren B. ACL injury reduces satellite cell abundance and promotes fibrogenic cell expansion within skeletal muscle. J Orthop Res. 2017;35(9):1876\u201385.","DOI":"10.1002\/jor.23502"},{"issue":"6","key":"4818_CR12","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1177\/0363546519832864","volume":"47","author":"BD Peck","year":"2019","unstructured":"Peck BD, Brightwell CR, Johnson DL, Ireland ML, Noehren B, Fry CS. Anterior cruciate ligament tear promotes skeletal muscle myostatin expression, fibrogenic cell expansion, and a decline in muscle quality. Am J Sports Med. 2019;47(6):1385\u201395.","journal-title":"Am J Sports Med"},{"key":"4818_CR13","doi-asserted-by":"publisher","DOI":"10.1177\/03635465221135769","author":"AR Keeble","year":"2022","unstructured":"Keeble AR, Brightwell CR, Latham CM, Thomas NT, Mobley CB, Murach KA, et al. Depressed protein synthesis and anabolic signaling potentiate ACL tear-resultant quadriceps atrophy. Am J Sports Med. 2022. https:\/\/doi.org\/10.1177\/03635465221135769.","journal-title":"Am J Sports Med"},{"key":"4818_CR14","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adi9134","author":"C Brightwell","year":"2023","unstructured":"Brightwell C, Latham C, Keeble A, Thomas N, Owen A, Reeves K, et al. GDF8 inhibition enhances musculoskeletal recovery and mitigates posttraumatic osteoarthritis following joint injury. Sci Adv. 2023. https:\/\/doi.org\/10.1126\/sciadv.adi9134.","journal-title":"Sci Adv"},{"key":"4818_CR15","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.freeradbiomed.2023.12.037","volume":"212","author":"CM Latham","year":"2023","unstructured":"Latham CM, Balawender PJ, Thomas NT, Keeble AR, Brightwell CR, Ismaeel A, et al. Overexpression of manganese superoxide dismutase mitigates ACL injury-induced muscle atrophy, weakness and oxidative damage. Free Radical Biol Med. 2023;212:191\u20138.","journal-title":"Free Radical Biol Med"},{"key":"4818_CR16","doi-asserted-by":"crossref","unstructured":"Keeble AR, Thomas NT, Balawender PJ, Brightwell CR, Gonzalez-Velez S, O'Daniel MG, et al. CSF1-R inhibition attenuates posttraumatic osteoarthritis and quadriceps atrophy following ligament injury. J Physiol. 2025;603(23):7549\u201366.","DOI":"10.1113\/JP286815"},{"key":"4818_CR17","doi-asserted-by":"publisher","DOI":"10.2106\/jbjs.16.00035","author":"B Noehren","year":"2016","unstructured":"Noehren B, Andersen A, Hardy P, Johnson DR, Ireland ML, Thompson KL, et al. Cellular and morphological alterations in the vastus lateralis muscle as the result of ACL injury and\u00a0reconstruction. J Bone Joint Surg. 2016. https:\/\/doi.org\/10.2106\/jbjs.16.00035.","journal-title":"J Bone Joint Surg"},{"key":"4818_CR18","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.3389\/fphys.2018.01343","volume":"9","author":"M Fl\u00fcck","year":"2018","unstructured":"Fl\u00fcck M, Viecelli C, Bapst AM, Kasper S, Valdivieso P, Franchi MV, et al. Knee Extensors Muscle Plasticity Over a 5-Years Rehabilitation Process After Open Knee Surgery. Front Physiol. 2018;9:1343.","journal-title":"Front Physiol"},{"issue":"3","key":"4818_CR19","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1002\/jor.25065","volume":"40","author":"TW Tourville","year":"2022","unstructured":"Tourville TW, Voigt TB, Choquette RH, Failla MJ, Endres NK, Slauterbeck JR, et al. Skeletal muscle cellular contractile dysfunction after anterior cruciate ligament reconstruction contributes to quadriceps weakness at 6-month follow-up. J Orthop Res. 2022;40(3):727\u201337.","journal-title":"J Orthop Res"},{"key":"4818_CR20","doi-asserted-by":"crossref","unstructured":"Gumucio JP, Sugg KB, Enselman ERS, Konja AC, Eckhardt LR, Bedi A, et al. Anterior cruciate ligament tear induces a sustained loss of muscle fiber force production. Muscle Nerve. 2018:10.1002\/mus.26075.","DOI":"10.1002\/mus.26075"},{"issue":"1","key":"4818_CR21","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1186\/s12939-022-01787-1","volume":"21","author":"J Ott","year":"2022","unstructured":"Ott J, Champagne SN, Bachani AM, Morgan R. Scoping \u201csex\u201d and \u201cgender\u201d in rehabilitation: (mis)representations and effects. Int J Equity Health. 2022;21(1):179.","journal-title":"Int J Equity Health"},{"issue":"7","key":"4818_CR22","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1016\/j.apmr.2024.01.026","volume":"105","author":"S Mehrabi","year":"2024","unstructured":"Mehrabi S, Harnett A, Saikaley M, Fleet JL, Eng JJ, Bayley M, et al. Female Enrollment in Rehabilitation Trials: A Systematic Review of Reporting Sex and Female Participation in Randomized Controlled Trials of Poststroke Upper Extremity Rehabilitation Over 50 Years. Arch Phys Med Rehabil. 2024;105(7):1399\u2013406.","journal-title":"Arch Phys Med Rehabil"},{"issue":"4","key":"4818_CR23","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1161\/CIRCRESAHA.121.319894","volume":"130","author":"JR Smith","year":"2022","unstructured":"Smith JR, Thomas RJ, Bonikowske AR, Hammer SM, Olson TP. Sex Differences in Cardiac Rehabilitation Outcomes. Circ Res. 2022;130(4):552\u201365.","journal-title":"Circ Res"},{"issue":"10","key":"4818_CR24","doi-asserted-by":"publisher","first-page":"2553","DOI":"10.1177\/0363546515595834","volume":"43","author":"PW Kline","year":"2015","unstructured":"Kline PW, Morgan KD, Johnson DL, Ireland ML, Noehren B. Impaired Quadriceps Rate of Torque Development and Knee Mechanics After Anterior Cruciate Ligament Reconstruction With Patellar Tendon Autograft. Am J Sports Med. 2015;43(10):2553\u20138.","journal-title":"Am J Sports Med"},{"key":"4818_CR25","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13278","author":"T Snijders","year":"2017","unstructured":"Snijders T, Nederveen JP, Verdijk LB, Houben AJHM, Goossens GH, Parise G, et al. Muscle fiber capillarization as determining factor on indices of insulin sensitivity in humans. Physiol Rep. 2017. https:\/\/doi.org\/10.14814\/phy2.13278.","journal-title":"Physiol Rep"},{"issue":"2","key":"4818_CR26","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1002\/jcsm.12137","volume":"8","author":"T Snijders","year":"2017","unstructured":"Snijders T, Nederveen JP, Joanisse S, Leenders M, Verdijk LB, van Loon LJ, et al. Muscle fibre capillarization is a critical factor in muscle fibre hypertrophy during resistance exercise training in older men. J Cachexia Sarcopenia Muscle. 2017;8(2):267\u201376.","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"4818_CR27","doi-asserted-by":"crossref","unstructured":"Wen Y, Murach KA, Vechetti IJ, Jr., Fry CS, Vickery C, Peterson CA, et al. MyoVision: software for automated high-content analysis of skeletal muscle immunohistochemistry. J Appl Physiol (1985). 2018;124(1):40\u201351.","DOI":"10.1152\/japplphysiol.00762.2017"},{"key":"4818_CR28","doi-asserted-by":"publisher","first-page":"110723","DOI":"10.1016\/j.exger.2019.110723","volume":"127","author":"T Moro","year":"2019","unstructured":"Moro T, Brightwell CR, Phalen DE, McKenna CF, Lane SJ, Porter C, et al. Low skeletal muscle capillarization limits muscle adaptation to resistance exercise training in older adults. Exp Gerontol. 2019;127:110723.","journal-title":"Exp Gerontol"},{"issue":"1","key":"4818_CR29","first-page":"60","volume":"47","author":"H Holth\u00f6fer","year":"1982","unstructured":"Holth\u00f6fer H, Virtanen I, Kariniemi AL, Hormia M, Linder E, Miettinen A. Ulex europaeus I lectin as a marker for vascular endothelium in human tissues. Lab Invest. 1982;47(1):60\u20136.","journal-title":"Lab Invest"},{"issue":"Pt 12","key":"4818_CR30","doi-asserted-by":"publisher","first-page":"2625","DOI":"10.1113\/jphysiol.2014.271288","volume":"592","author":"CS Fry","year":"2014","unstructured":"Fry CS, Noehren B, Mula J, Ubele MF, Westgate PM, Kern PA, et al. Fibre type-specific satellite cell response to aerobic training in sedentary adults. J Physiol. 2014;592(Pt 12):2625\u201335.","journal-title":"J Physiol"},{"issue":"1","key":"4818_CR31","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","volume":"12","author":"S Jin","year":"2021","unstructured":"Jin S, Guerrero-Juarez CF, Zhang L, Chang I, Ramos R, Kuan CH, et al. Inference and analysis of cell-cell communication using Cell Chat. Nat Commun. 2021;12(1):1088.","journal-title":"Nat Commun"},{"issue":"10","key":"4818_CR32","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1161\/CIRCRESAHA.123.323161","volume":"133","author":"CG Pass","year":"2023","unstructured":"Pass CG, Palzkill V, Tan J, Kim K, Thome T, Yang Q, et al. Single-Nuclei RNA-Sequencing of the Gastrocnemius Muscle in Peripheral Artery Disease. Circ Res. 2023;133(10):791\u2013809.","journal-title":"Circ Res"},{"key":"4818_CR33","doi-asserted-by":"crossref","unstructured":"Karlsen A, Yeung CC, Schjerling P, Denz L, Hoegsbjerg C, Jakobsen JR, et al. Distinct myofibre domains of the human myotendinous junction revealed by single-nucleus RNA sequencing. J Cell Sci. 2023;136(8):jcs260913.","DOI":"10.1242\/jcs.260913"},{"issue":"4","key":"4818_CR34","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.cels.2019.03.003","volume":"8","author":"CS McGinnis","year":"2019","unstructured":"McGinnis CS, Murrow LM, Gartner ZJ. DoubletFinder: doublet detection in single-cell RNA sequencing data using artificial nearest neighbors. Cell Syst. 2019;8(4):329-37.e4.","journal-title":"Cell Syst"},{"issue":"1","key":"4818_CR35","doi-asserted-by":"publisher","first-page":"6374","DOI":"10.1038\/s41467-020-20063-w","volume":"11","author":"MJ Petrany","year":"2020","unstructured":"Petrany MJ, Swoboda CO, Sun C, Chetal K, Chen X, Weirauch MT, et al. Single-nucleus RNA-seq identifies transcriptional heterogeneity in multinucleated skeletal myofibers. Nat Commun. 2020;11(1):6374.","journal-title":"Nat Commun"},{"issue":"1","key":"4818_CR36","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.1038\/s41467-020-15816-6","volume":"11","author":"B Jew","year":"2020","unstructured":"Jew B, Alvarez M, Rahmani E, Miao Z, Ko A, Garske KM, et al. Accurate estimation of cell composition in bulk expression through robust integration of single-cell information. Nat Commun. 2020;11(1):1971.","journal-title":"Nat Commun"},{"issue":"1","key":"4818_CR37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2165\/00007256-199928010-00001","volume":"28","author":"SD Barber-Westin","year":"1999","unstructured":"Barber-Westin SD, Noyes FR. Assessment of sports participation levels following knee injuries. Sports Med. 1999;28(1):1\u201310.","journal-title":"Sports Med"},{"issue":"Suppl 76","key":"4818_CR38","first-page":"16","volume":"15","author":"J Bergstrom","year":"1963","unstructured":"Bergstrom J. Clinical studies on cell electrolytes. Scand J Clin Lab Invest. 1963;15(Suppl 76):16\u20138.","journal-title":"Scand J Clin Lab Invest"},{"issue":"7","key":"4818_CR39","doi-asserted-by":"publisher","first-page":"609","DOI":"10.3109\/00365517509095787","volume":"35","author":"J Bergstrom","year":"1975","unstructured":"Bergstrom J. Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand J Clin Lab Invest. 1975;35(7):609\u201316.","journal-title":"Scand J Clin Lab Invest"},{"key":"4818_CR40","doi-asserted-by":"crossref","unstructured":"Wen Y, Latham CM, Moore AN, Thomas NT, Lancaster BD, Reeves KA, et al. Vitamin D status associates with skeletal muscle loss after anterior cruciate ligament reconstruction. JCI Insight. 2023;8(23):e170518.","DOI":"10.1172\/jci.insight.170518"},{"issue":"6","key":"4818_CR41","doi-asserted-by":"publisher","first-page":"e000459","DOI":"10.1161\/JAHA.113.000459","volume":"2","author":"JR Manning","year":"2013","unstructured":"Manning JR, Yin G, Kaminski CN, Magyar J, Feng HZ, Penn J, et al. Rad GTPase deletion increases L-type calcium channel current leading to increased cardiac contraction. J Am Heart Assoc. 2013;2(6):e000459.","journal-title":"J Am Heart Assoc"},{"issue":"9","key":"4818_CR42","doi-asserted-by":"publisher","first-page":"2519","DOI":"10.1089\/ars.2011.3973","volume":"15","author":"SK Powers","year":"2011","unstructured":"Powers SK, Smuder AJ, Criswell DS. Mechanistic links between oxidative stress and disuse muscle atrophy. Antioxid Redox Signal. 2011;15(9):2519\u201328.","journal-title":"Antioxid Redox Signal"},{"issue":"Pt 9","key":"4818_CR43","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.1113\/jphysiol.2010.203232","volume":"589","author":"MA Pellegrino","year":"2011","unstructured":"Pellegrino MA, Desaphy JF, Brocca L, Pierno S, Camerino DC, Bottinelli R. Redox homeostasis, oxidative stress and disuse muscle atrophy. J Physiol. 2011;589(Pt 9):2147\u201360.","journal-title":"J Physiol"},{"issue":"10","key":"4818_CR44","doi-asserted-by":"publisher","first-page":"17727","DOI":"10.1002\/jcp.28398","volume":"234","author":"C Yang","year":"2019","unstructured":"Yang C, You D, Huang J, Yang B, Huang X, Ni J. Effects of AURKA-mediated degradation of SOD2 on mitochondrial dysfunction and cartilage homeostasis in osteoarthritis. J Cell Physiol. 2019;234(10):17727\u201338.","journal-title":"J Cell Physiol"},{"key":"4818_CR45","doi-asserted-by":"publisher","first-page":"101950","DOI":"10.1016\/j.redox.2021.101950","volume":"41","author":"D Ross","year":"2021","unstructured":"Ross D, Siegel D. The diverse functionality of NQO1 and its roles in redox control. Redox Biol. 2021;41:101950.","journal-title":"Redox Biol"},{"issue":"4","key":"4818_CR46","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1002\/ana.410420416","volume":"42","author":"MF Beal","year":"1997","unstructured":"Beal MF, Ferrante RJ, Browne SE, Matthews RT, Kowall NW, Brown RH. Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis. Ann Neurol. 1997;42(4):644\u201354.","journal-title":"Ann Neurol"},{"key":"4818_CR47","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.brainres.2007.05.076","volume":"1164","author":"W Tripanichkul","year":"2007","unstructured":"Tripanichkul W, Sripanichkulchai K, Duce JA, Finkelstein DI. 17Beta-estradiol reduces nitrotyrosine immunoreactivity and increases SOD1 and SOD2 immunoreactivity in nigral neurons in male mice following MPTP insult. Brain Res. 2007;1164:24\u201331.","journal-title":"Brain Res"},{"issue":"2","key":"4818_CR48","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1080\/10715769800300111","volume":"29","author":"MV Kumari","year":"1998","unstructured":"Kumari MV, Hiramatsu M, Ebadi M. Free radical scavenging actions of metallothionein isoforms I and II. Free Radic Res. 1998;29(2):93\u2013101.","journal-title":"Free Radic Res"},{"issue":"17","key":"4818_CR49","doi-asserted-by":"publisher","first-page":"6624","DOI":"10.1073\/pnas.87.17.6624","volume":"87","author":"DJ Good","year":"1990","unstructured":"Good DJ, Polverini PJ, Rastinejad F, Le Beau MM, Lemons RS, Frazier WA, et al. A tumor suppressor-dependent inhibitor of angiogenesis is immunologically and functionally indistinguishable from a fragment of thrombospondin. Proc Natl Acad Sci U S A. 1990;87(17):6624\u20138.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"4818_CR50","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1016\/0006-291X(90)92171-U","volume":"170","author":"P Bagavandoss","year":"1990","unstructured":"Bagavandoss P, Wilks JW. Specific inhibition of endothelial cell proliferation by thrombospondin. Biochem Biophys Res Commun. 1990;170(2):867\u201372.","journal-title":"Biochem Biophys Res Commun"},{"issue":"6","key":"4818_CR51","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1016\/j.jvs.2006.07.051","volume":"44","author":"N Yamada","year":"2006","unstructured":"Yamada N, Li W, Ihaya A, Kimura T, Morioka K, Uesaka T, et al. Platelet-derived endothelial cell growth factor gene therapy for limb ischemia. J Vasc Surg. 2006;44(6):1322\u20138.","journal-title":"J Vasc Surg"},{"issue":"6216","key":"4818_CR52","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/338557a0","volume":"338","author":"F Ishikawa","year":"1989","unstructured":"Ishikawa F, Miyazono K, Hellman U, Drexler H, Wernstedt C, Hagiwara K, et al. Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor. Nature. 1989;338(6216):557\u201362.","journal-title":"Nature"},{"issue":"4","key":"4818_CR53","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1177\/0363546504269937","volume":"33","author":"J Agel","year":"2005","unstructured":"Agel J, Arendt EA, Bershadsky B. Anterior cruciate ligament injury in national collegiate athletic association basketball and soccer: a 13-year review. Am J Sports Med. 2005;33(4):524\u201330.","journal-title":"Am J Sports Med"},{"issue":"4","key":"4818_CR54","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1152\/physrev.00031.2007","volume":"88","author":"SK Powers","year":"2008","unstructured":"Powers SK, Jackson MJ. Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev. 2008;88(4):1243\u201376.","journal-title":"Physiol Rev"},{"issue":"Pt 2","key":"4818_CR55","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.freeradbiomed.2023.10.393","volume":"209","author":"V Galvan-Alvarez","year":"2023","unstructured":"Galvan-Alvarez V, Gallego-Selles A, Martinez-Canton M, Garc\u00eda-Gonzalez E, Gelabert-Rebato M, Ponce-Gonzalez JG, et al. Antioxidant enzymes and Nrf2\/Keap1 in human skeletal muscle: Influence of age, sex, adiposity and aerobic fitness. Free Radical Biol Med. 2023;209(Pt 2):282\u201391.","journal-title":"Free Radical Biol Med"},{"key":"4818_CR56","doi-asserted-by":"crossref","unstructured":"Tsitkanou S, Morena da Silva F, Cabrera AR, Schrems ER, Murach KA, Washington TA, et al. Biological sex divergence in transcriptomic profiles during the onset of hindlimb unloading-induced atrophy. Am J Physiol Cell Physiol. 2023;325(5):C1276-C93.","DOI":"10.1152\/ajpcell.00352.2023"},{"key":"4818_CR57","doi-asserted-by":"publisher","first-page":"804","DOI":"10.3389\/fphys.2019.00804","volume":"10","author":"EJ Goldberg","year":"2019","unstructured":"Goldberg EJ, Schmidt CA, Green TD, Karnekar R, Yamaguchi DJ, Spangenberg EE, et al. Temporal association between ischemic muscle perfusion recovery and the restoration of muscle contractile function after hindlimb ischemia. Front Physiol. 2019;10:804.","journal-title":"Front Physiol"},{"issue":"Pt 8","key":"4818_CR58","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1113\/jphysiol.2008.164384","volume":"587","author":"IM Olfert","year":"2009","unstructured":"Olfert IM, Howlett RA, Tang K, Dalton ND, Gu Y, Peterson KL, et al. Muscle-specific VEGF deficiency greatly reduces exercise endurance in mice. J Physiol. 2009;587(Pt 8):1755\u201367.","journal-title":"J Physiol"},{"issue":"2","key":"4818_CR59","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1152\/japplphysiol.00638.2015","volume":"120","author":"KA Huey","year":"2016","unstructured":"Huey KA, Smith SA, Sulaeman A, Breen EC. Skeletal myofiber VEGF is necessary for myogenic and contractile adaptations to functional overload of the plantaris in adult mice. J Appl Physiol (1985). 2016;120(2):188\u201395.","journal-title":"J Appl Physiol (1985)"},{"issue":"Pt 1","key":"4818_CR60","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1113\/jphysiol.2006.108720","volume":"574","author":"C Roepstorff","year":"2006","unstructured":"Roepstorff C, Thiele M, Hillig T, Pilegaard H, Richter EA, Wojtaszewski JF, et al. Higher skeletal muscle alpha2AMPK activation and lower energy charge and fat oxidation in men than in women during submaximal exercise. J Physiol. 2006;574(Pt 1):125\u201338.","journal-title":"J Physiol"},{"key":"4818_CR61","doi-asserted-by":"publisher","first-page":"102439","DOI":"10.1016\/j.ceca.2021.102439","volume":"98","author":"DR Miranda","year":"2021","unstructured":"Miranda DR, Voss AA, Bannister RA. Into the spotlight: RGK proteins in skeletal muscle. Cell Calcium. 2021;98:102439.","journal-title":"Cell Calcium"},{"issue":"9","key":"4818_CR62","doi-asserted-by":"publisher","first-page":"1950","DOI":"10.1016\/j.bpj.2014.03.033","volume":"106","author":"D Beqollari","year":"2014","unstructured":"Beqollari D, Romberg CF, Meza U, Papadopoulos S, Bannister RA. Differential effects of RGK proteins on L-type channel function in adult mouse skeletal muscle. Biophys J. 2014;106(9):1950\u20137.","journal-title":"Biophys J"},{"issue":"48","key":"4818_CR63","doi-asserted-by":"publisher","first-page":"eadi9134","DOI":"10.1126\/sciadv.adi9134","volume":"9","author":"CR Brightwell","year":"2023","unstructured":"Brightwell CR, Latham CM, Keeble AR, Thomas NT, Owen AM, Reeves KA, et al. GDF8 inhibition enhances musculoskeletal recovery and mitigates posttraumatic osteoarthritis following joint injury. Sci Adv. 2023;9(48):eadi9134.","journal-title":"Sci Adv"},{"key":"4818_CR64","doi-asserted-by":"publisher","unstructured":"Garcia SM, Lau J, Wague A, Sharma S, Wang KC, Lizarraga M, et al. Sex-Based Differences in Cell Types and Gene Expression within the Anterior Cruciate Ligament. J Bone Joint Surg Am. 2026. https:\/\/doi.org\/10.2106\/JBJS.25.00860.","DOI":"10.2106\/JBJS.25.00860"},{"key":"4818_CR65","unstructured":"Keeble AR, Owen AM, Thomas NT, Gonzalez-Velez S, Brightwell CR, Barnes T, et al. RNA-sequencing analysis of human skeletal muscle following ACL injury. NCBI Gene Expression Omnibus (GEO). http:\/\/identifiers.org\/geo:GSE314430. (2026)."},{"key":"4818_CR66","unstructured":"Keeble AR, Owen AM, Thomas NT, Gonzalez-Velez S, Brightwell CR, Barnes T, et al. RNA-sequencing analysis of human skeletal muscle following ACL reconstruction. NCBI Gene Expression Omnibus (GEO). http:\/\/identifiers.org\/geo:GSE324033. (2026)."},{"key":"4818_CR67","unstructured":"Keeble AR, Owen AM, Thomas NT, Gonzalez-Velez S, Brightwell CR, Barnes T, et al. Single nucleus RNA-sequencing analysis of human skeletal muscle following ACL reconstruction. NCBI Gene Expression Omnibus (GEO). http:\/\/identifiers.org\/geo:GSE270868. (2026)."}],"container-title":["BMC Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12916-026-04818-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-026-04818-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-026-04818-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T19:03:14Z","timestamp":1778007794000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12916-026-04818-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,26]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4818"],"URL":"https:\/\/doi.org\/10.1186\/s12916-026-04818-8","relation":{},"ISSN":["1741-7015"],"issn-type":[{"value":"1741-7015","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,26]]},"assertion":[{"value":"15 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Institutional Review Board (#43046) at the University of Kentucky and performed in accordance with the ethical standards of the 1964 Declaration of Helsinki. Informed written consent was obtained from each patient or guardian before participation in this study. Additionally, all minors in this study assented to participation.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"AVS has received fellowship support from Smith & Nephew and Arthrex in addition to consulting fees from Smith and Nephew, Bioventus, Allosource, and Vericel. DLJ has received travel expenses from Linvatec, in addition to consulting fees from Smith\u2009+\u2009Nephew and from Xiros Inc. YW is the founder of MyoAnalytics, LLC. The authors declare no other competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"287"}}