{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T03:06:14Z","timestamp":1789268774140,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T00:00:00Z","timestamp":1618876800000},"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":["R01 AR072615"],"award-info":[{"award-number":["R01 AR072615"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007588","name":"Washington State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007588","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Rheumatoid arthritis synovial fibroblasts (RASFs) are crucial mediators of synovial inflammation and joint destruction. However, their intrinsic immunoregulatory mechanisms under chronic inflammation remain unclear. Thus, the present study was undertaken to understand the role of a newly identified GTPase, guanylate binding protein 5 (GBP\u20105), in RA pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The expression of <jats:italic>GBP1<\/jats:italic>\u2013<jats:italic>GBP7<\/jats:italic> transcripts was evaluated using quantitative reverse transcription\u2013polymerase chain reaction in RA synovial tissue or synovial tissue unaffected by RA. Our investigation on transient small interfering RNA (siRNA) knockdown and lentiviral overexpression in human RASFs examined the regulatory role of GBP\u20105 on proinflammatory cytokine signaling pathways. Unbiased whole transcriptome RNA sequencing analysis was used to assess the impact of GBP\u20105 on RASF molecular functions. These findings were confirmed using a rat model of adjuvant\u2010induced arthritis (AIA) in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among different GBPs evaluated, GBP\u20105 was selectively up\u2010regulated in RA synovial tissue (<jats:italic>P<\/jats:italic> &lt; 0.05; n\u00a0= 4) and in the joints of rats with AIA (<jats:italic>P<\/jats:italic> &lt; 0.05; n = 6) and was significantly induced in human RASFs by interleukin\u20101\u03b2 (IL\u20101\u03b2), tumor necrosis factor (TNF), and\/or interferon\u2010\u03b3 (IFN\u03b3) (<jats:italic>P<\/jats:italic> &lt; 0.05; n = 3). Bioinformatics analysis of RNA sequencing data identified cytokine\u2013cytokine receptor signaling as a major function altered by GBP\u20105, with IL\u20106 signaling as a primary target. Knockdown of GBP\u20105 amplified IL\u20101\u03b2\u2013induced IL\u20106, IL\u20108, and epithelial neutrophil\u2013activating peptide 78\/CXCL5 production by 44%, 54%, 45%, respectively, and matrix metalloproteinase 1 (MMP\u20101) production by several\u2010fold\u2014effects that reversed with exogenously delivered GBP\u20105. Lack of GBP\u20105 increased IFN\u03b3\u2010induced proliferation and migration of human RASFs. GBP\u20105 knockdown in vivo using intraarticular siRNA exacerbated disease onset, severity, synovitis, and bone destruction in rat AIA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Expressed by RASFs in response to cytokine stimulation, GBP\u20105 has potential to restore cellular homeostasis and blunt inflammation and tissue destruction in RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41611","type":"journal-article","created":{"date-parts":[[2020,12,5]],"date-time":"2020-12-05T05:24:57Z","timestamp":1607145897000},"page":"943-954","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Regulation of Synovial Inflammation and Tissue Destruction by Guanylate Binding Protein 5 in Synovial Fibroblasts From Patients With Rheumatoid Arthritis and Rats With Adjuvant\u2010Induced Arthritis"],"prefix":"10.1002","volume":"73","author":[{"given":"Mahamudul","family":"Haque","sequence":"first","affiliation":[{"name":"Washington State University College of Pharmacy  Spokane"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil K.","family":"Singh","sequence":"additional","affiliation":[{"name":"Washington State University College of Pharmacy  Spokane"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhu M.","family":"Ouseph","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine  Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2526-8110","authenticated-orcid":false,"given":"Salahuddin","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Washington State University College of Pharmacy, Spokane, and University of Washington School of Medicine  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