{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:32:42Z","timestamp":1790947962551,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,12,27]],"date-time":"2018-12-27T00:00:00Z","timestamp":1545868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C17199\/A18246"],"award-info":[{"award-number":["C17199\/A18246"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2019,1]]},"abstract":"\n Objective<\/jats:title>\n \n A major characteristic of the autoimmune disease primary Sj\u00f6gren's syndrome (\n SS<\/jats:styled-content>\n ) is salivary gland (\n SG<\/jats:styled-content>\n ) hypofunction. The inability of resident\n SG<\/jats:styled-content>\n stem cells (\n SGSC<\/jats:styled-content>\n s) to maintain homeostasis and saliva production has never been explained and limits our comprehension of mechanisms underlying primary\n SS<\/jats:styled-content>\n . The present study was undertaken to investigate the role of salivary gland stem cells in hyposalivation in primary SS.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n SGSC<\/jats:styled-content>\n s were isolated from parotid biopsy samples from controls and patients classified as having primary\n SS<\/jats:styled-content>\n or incomplete primary\n SS<\/jats:styled-content>\n , according to the American College of Rheumatology\/European League Against Rheumatism criteria. Self\u2010renewal and differentiation assays were used to determine\n SGSC<\/jats:styled-content>\n regenerative potential,\n RNA<\/jats:styled-content>\n was extracted for sequencing analysis, single telomere length analysis was conducted to determine telomere length, and frozen tissue samples were used for immunohistochemical analysis.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n SGSC<\/jats:styled-content>\n s isolated from primary\n SS<\/jats:styled-content>\n parotid gland biopsy samples were regeneratively inferior to healthy control specimens. We demonstrated that\n SGSC<\/jats:styled-content>\n s from samples from patients with primary\n SS<\/jats:styled-content>\n are not only lower in number and less able to differentiate, but are likely to be senescent, as revealed by telomere length analysis,\n RNA<\/jats:styled-content>\n sequencing, and immunostaining. We further found that\n SGSC<\/jats:styled-content>\n s exposed to primary\n SS<\/jats:styled-content>\n \u2013associated proinflammatory cytokines we induced to proliferate, express senescence\u2010associated genes, and subsequently differentiate into intercalated duct cells. We also localized p16+ senescent cells to the intercalated ducts in primary\n SS SG<\/jats:styled-content>\n tissue, suggesting a block in\n SGSC<\/jats:styled-content>\n differentiation into acinar cells.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n This study represents the first characterization of\n SGSC<\/jats:styled-content>\n s in primary\n SS<\/jats:styled-content>\n , and also the first demonstration of a linkage between an autoimmune disease and a parenchymal premature\u2010aging phenotype. The knowledge garnered in this study indicates that disease\u2010modifying antirheumatic drugs used to treat primary\n SS<\/jats:styled-content>\n are not likely to restore saliva production, and should be supplemented with fresh\n SGSC<\/jats:styled-content>\n s to recover saliva production.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.40659","type":"journal-article","created":{"date-parts":[[2018,7,9]],"date-time":"2018-07-09T03:04:51Z","timestamp":1531105491000},"page":"133-142","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Salivary Gland Stem Cells Age Prematurely in Primary Sj\u00f6gren's Syndrome"],"prefix":"10.1002","volume":"71","author":[{"given":"Sarah","family":"Pringle","sequence":"first","affiliation":[{"name":"University of Groningen and University Medical Center Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Wang","sequence":"additional","affiliation":[{"name":"University of Groningen and University Medical Center Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwenny M. P. J.","family":"Verstappen","sequence":"additional","affiliation":[{"name":"University of Groningen and University Medical Center Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneke H.","family":"Terpstra","sequence":"additional","affiliation":[{"name":"University of Groningen and University Medical Center Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarence K.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb Lawrence Township New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiqing","family":"He","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb Pennington New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Patel","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb Pennington New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhiannon E.","family":"Jones","sequence":"additional","affiliation":[{"name":"Cardiff University School of Medicine Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duncan M.","family":"Baird","sequence":"additional","affiliation":[{"name":"Cardiff University School of Medicine Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred K. 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M.","family":"Kroese","sequence":"additional","affiliation":[{"name":"University of Groningen and University Medical Center Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23177"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1586\/1744666X.2014.891439"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/32.7.578"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kel067"},{"key":"e_1_2_8_6_1","first-page":"1905","article-title":"Clinical course of primary Sj\u00f6gren's syndrome: salivary, oral, and serologic aspects","volume":"27","author":"Gannot G","year":"2000","journal-title":"J 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