{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:19:50Z","timestamp":1790767190055,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,7,30]],"date-time":"2014-07-30T00:00:00Z","timestamp":1406678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR49823"],"award-info":[{"award-number":["AR49823"]}],"id":[{"id":"10.13039\/100000069","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":["AR063596"],"award-info":[{"award-number":["AR063596"]}],"id":[{"id":"10.13039\/100000069","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":["AR056950"],"award-info":[{"award-number":["AR056950"]}],"id":[{"id":"10.13039\/100000069","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":[[2014,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Fibrosis of the subsynovial connective tissue (SSCT) is a predominant feature of carpal tunnel syndrome (CTS). While the nature of CTS has been extensively studied, little is known about the etiology of this disease. We investigated SSCT tissue from patients with CTS and control subjects using fibrosis arrays and cell culture analysis. Twofold changes in fibrotic gene expression were found in multiple genes from patient SSCT using fibrosis arrays. This data was confirmed via qRT\u2010PCR on a subset of genes; collagen I (Col1), collagen III (Col3), connective tissue growth factor (CTGF), transforming growth factor \u03b2 (TGF\u2010\u03b2), and SMAD3 (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) which significantly corroborate the fold changes found in the fibrosis arrays. To further explore the nature of SSCT fibrosis, cells were isolated from patient and control tissue. Col1, Col3, TGF\u2010\u03b2, and SMAD3 were highly expressed in patient SSCT fibroblasts as compared to control (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Further, fibrotic genes expression was decreased by inhibiting TGF\u2010\u03b2 receptor I (T\u03b2RI) activity (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). TGF\u2010\u03b2 second messenger SMAD activity was significantly activated in SSCT fibroblasts from patients and this activation was abrogated by inhibiting T\u03b2RI signaling (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). These findings suggest that blocking TGF\u2010\u03b2 signaling may be an important therapeutic approach to treating the underlying fibrosis of SSCT in CTS patients. \u00a9 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1444\u20131450, 2014.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jor.22694","type":"journal-article","created":{"date-parts":[[2014,7,30]],"date-time":"2014-07-30T10:37:36Z","timestamp":1406716656000},"page":"1444-1450","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["TGF\u2010\u03b2 signaling regulates fibrotic expression and activity in carpal tunnel syndrome"],"prefix":"10.1002","volume":"32","author":[{"given":"Anne","family":"Gingery","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Biomechanics and Tendon &amp; Soft Tissue Biology Laboratory Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai\u2010Hua","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Biomechanics and Tendon &amp; Soft Tissue Biology Laboratory Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra M.","family":"Passe","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Biomechanics and Tendon &amp; Soft Tissue Biology Laboratory Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai\u2010Nan","family":"An","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Biomechanics and Tendon &amp; Soft Tissue Biology Laboratory Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunfeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Biomechanics and Tendon &amp; Soft Tissue Biology Laboratory Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Amadio","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Biomechanics and Tendon &amp; Soft Tissue Biology Laboratory Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,7,30]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0266-7681(92)90091-F"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.5414\/NPP28129"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0363-5023(91)90208-S"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0363-5023(90)90070-8"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11552-006-9009-z"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.22485"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.I.00643"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.I.00642"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700669"},{"key":"e_1_2_5_11_1","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1186\/1755-1536-5-S1-S2","article-title":"Developmental responses to lung injury: repair or fibrosis","volume":"5","author":"Warburton D.","year":"2012","journal-title":"Fibrogenesis Tissue Repair"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0350661"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.3109\/08977194.2011.595411"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21725"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019429"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204812200"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-200407000-00014"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21163"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21565"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2012.10.003"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3810"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.111.1.131"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.67.1.753"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2002.01641.x"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100754200"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758-5996-5-48"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2012.07.006"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.135.5.1887"},{"key":"e_1_2_5_29_1","first-page":"115","article-title":"Signaling in fibrosis: targeting the TGF beta, endothelin\u20101 and CCN2 axis in scleroderma","volume":"1","author":"Leask A.","year":"2009","journal-title":"Front Biosci (Elite Ed)"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ken278"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.478685"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.E.00377"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006743"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23102"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb826"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2005.10.005"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21449"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199910)181:1<153::AID-JCP16>3.0.CO;2-K"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200102)44:2<474::AID-ANR67>3.0.CO;2-#"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-12-113"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etp.2013.02.003"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(97)00010-5"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e32835b137b"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvs089"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-3217com"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00776.x"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543780903382609"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23564"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjor.22694","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.22694","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T11:17:00Z","timestamp":1696331820000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.22694"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7,30]]},"references-count":47,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2014,11]]}},"alternative-id":["10.1002\/jor.22694"],"URL":"https:\/\/doi.org\/10.1002\/jor.22694","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,30]]},"assertion":[{"value":"2014-02-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-06-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-07-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}