{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:28:54Z","timestamp":1790512134018,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG46927"],"award-info":[{"award-number":["AG46927"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG15768"],"award-info":[{"award-number":["AG15768"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AR075773"],"award-info":[{"award-number":["R01AR075773"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AR071582"],"award-info":[{"award-number":["R21AR071582"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In response to chronic injury, the muscles of the rotator cuff (RC) experience a unique degeneration characterized by extensive fatty infiltration and loss of contractile function. Human studies suggest this degeneration is also a feature of RC sarcopenia and may precede RC injury. In this study, we investigated whether RC muscles exhibit a similar unique sarcopenia in the mouse.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male and female mice were subdivided into four age groups: 3, 9, 18, and 24\u00a0months. The supraspinatus (SS) and infraspinatus muscles of the RC and the tibialis anterior (TA) muscle of the hindlimb were assessed. Muscle mass, contractile function, fibre cross\u2010sectional areas and numbers, fatty infiltration, and fibrosis were assessed at each time point. Targeted transcriptional analyses were performed to assess the role of metabolic and inflammatory derangement in the pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The 24\u2010month\u2010aged female mice exhibited decreased mass (25% lower than at 9 and 18\u00a0months, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) in all muscles tested. However, only RC muscles also exhibited decreased contractile tension at this time point (20% lower than at 18\u00a0months, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.005). Similarly, only female RC muscles exhibited increased fatty infiltration at 24\u00a0months (20% higher than 9\u00a0months, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and had elevated transcriptional markers of adipogenesis (2.4\u2010fold higher Pparg and 3.8\u2010fold higher Adipoq expression compared with 9\u00a0months, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Unbiased metabolic transcriptional profiling identified up\u2010regulation of the antigen presentation (<jats:italic>Z<\/jats:italic> scores of 2.3 and 1.9 for SS and TA, respectively) and cytokine and chemokine signalling (<jats:italic>Z<\/jats:italic> scores of 3.1 and 2.4 for SS and TA, respectively) pathways in 24\u00a0month female muscle compared with 9. Further transcriptional analysis supported increased expression of pro\u2010adipogenic inflammatory signals (6.3\u2010fold increase in Il6 and 5.0\u2010fold increase in Anxa2, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and increased presence of fibro\u2010adipogenic progenitors (2.5\u2010fold) in the 24\u2010month\u2010aged female RC compared with 9\u00a0months that together exacerbate fatty infiltration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data indicate that female mice replicate the unique sarcopenic pathology in the ageing human RC. Furthermore, they suggest that the exacerbated fatty infiltration is due to an interaction between higher resident fibro\u2010adipogenic progenitor numbers and an elevated systemic inflammation in aged female mice. We conclude that female mouse RC muscle is a novel system to study both human RC degeneration and the signals that regulate sarcopenic fatty infiltration in general, which is prevalent in humans but largely absent from the rodent hindlimb.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12808","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T07:42:47Z","timestamp":1635406967000},"page":"561-573","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A unique sarcopenic progression in the mouse rotator cuff"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9268-3993","authenticated-orcid":false,"given":"Gretchen A.","family":"Meyer","sequence":"first","affiliation":[{"name":"Program in Physical Therapy Washington University  St. Louis MO USA"},{"name":"Departments of Orthopaedic Surgery, Neurology and Biomedical Engineering Washington University  St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen C.","family":"Shen","sequence":"additional","affiliation":[{"name":"Program in Physical Therapy Washington University  St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/2309499016684318"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.16.00770"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-010-1689-6"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2522\/ptj.20150029"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0363546506297539"},{"key":"e_1_2_7_7_1","first-page":"30","article-title":"Prognostic factors affecting anatomic outcome of rotator cuff repair and correlation with functional outcome","volume":"25","author":"Oh 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