{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T15:30:53Z","timestamp":1789831853633,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T00:00:00Z","timestamp":1638662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"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>Degeneration of shoulder muscle tissues often result in tearing, causing pain, disability and loss of independence. Differential muscle involvement patterns have been reported in tears of shoulder muscles, yet the molecules involved in this pathology are poorly understood. The spatial distribution of biomolecules across the affected tissue can be accurately obtained with matrix\u2010assisted laser desorption\/ionization mass spectrometry imaging (MALDI\u2010MSI). The goal of this pilot study was to decipher the metabolic landscape across shoulder muscle tissues and to identify signatures of degenerated muscles in chronic conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Paired biopsies of two rotator cuff muscles, torn infraspinatus and intact teres minor, together with an intact shoulder muscle, the deltoid, were collected during an open tendon transfer surgery. Five patients, average age 65.2\u00a0\u00b1\u00a03.8\u00a0years, were selected for spatial metabolic profiling using high\u2010spatial resolution (MALDI\u2010TOF) and high\u2010mass resolution (MALDI\u2010FTICR) MSI in negative or positive ion mode. Metabolic signatures were identified using data\u2010driven analysis. Verifications of spatial localization for selected metabolic signatures were carried out using antibody immunohistology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Data\u2010driven analysis revealed major metabolic differences between intact and degenerated regions across all muscles. The area of degenerated regions, encompassed of fat, inflammation and fibrosis, significantly increased in both rotator cuff muscles, teres minor (27.9%) and infraspinatus (22.8%), compared with the deltoid (8.7%). The intact regions were characterized by 49 features, among which lipids were recognized. Several of the identified lipids were specifically enriched in certain myofiber types. Degenerated regions were specifically marked by the presence of 37 features. Heme was the most abundant metabolite in degenerated regions, whereas Heme oxygenase\u20101 (HO\u20101), which catabolizes heme, was found in intact regions. Higher HO\u20101 levels correlated with lower heme accumulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Degenerated regions are distinguished from intact regions by their metabolome profile. A muscle\u2010specific metabolome profile was not identified. The area of tissue degeneration significantly differs between the three examined muscles. Higher HO\u20101 levels in intact regions concurred with lower heme levels in degenerated regions. Moreover, HO\u20101 levels discriminated between dysfunctional and functional rotator cuff muscles. Additionally, the enrichment of specific lipids in certain myofiber types suggests that lipid metabolism differs between myofiber types. The signature metabolites can open options to develop personalized treatments for chronic shoulder muscles degeneration.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12873","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T01:26:40Z","timestamp":1638754000000},"page":"532-543","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["The metabolic landscape in chronic rotator cuff tear reveals tissue\u2010region\u2010specific signatures"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2543-8255","authenticated-orcid":false,"given":"Cyriel Sebastiaan","family":"Olie","sequence":"first","affiliation":[{"name":"Human Genetics Department Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"van Zeijl","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma","family":"el Abdellaoui","sequence":"additional","affiliation":[{"name":"Human Genetics Department Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjen","family":"Kolk","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celeste","family":"Overbeek","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1228-4162","authenticated-orcid":false,"given":"Rob G.H.H.","family":"Nelissen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6328-9305","authenticated-orcid":false,"given":"Bram","family":"Heijs","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3152-1952","authenticated-orcid":false,"given":"Vered","family":"Raz","sequence":"additional","affiliation":[{"name":"Human Genetics Department Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12238"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0304-3959(02)00372-x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/03009742.2011.605390"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.5312\/wjo.v6.i11.902"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-014-0476-x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-013-2204-y"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2015.00236"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0108-4"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcme.2015.10.001"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.25"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2017.01.004"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.anchem.1.031207.112841"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijms.2012.07.008"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201500536"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13361-015-1133-y"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201400088"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-30990-w"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12498"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-017-0143-9"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.95B4.30390"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/20.7_ts.661"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-018-1216-2"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2016.09.020"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1089"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humov.2018.10.003"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5667"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)00903-5"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3530459"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.3164\/jcbn.08-210-HO"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005803"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/4617801"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2013.02.008"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1106"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2017.10.017"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7435"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00115"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2017.01.001"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12144"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2017.04.006"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2019.06.020"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.8319"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr200280p"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-018-0010-6"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.7b04733"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.12873","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.12873","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.12873","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T23:56:12Z","timestamp":1692489372000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.12873"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,5]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["10.1002\/jcsm.12873"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.12873","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,5]]},"assertion":[{"value":"2021-02-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}