{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T21:46:44Z","timestamp":1774302404144,"version":"3.50.1"},"reference-count":74,"publisher":"Wiley","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["12-04-00038a"],"award-info":[{"award-number":["12-04-00038a"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["International Journal of Rheumatology"],"published-print":{"date-parts":[[2013]]},"abstract":"<jats:p>We evaluated changes in gene expression of<jats:italic>mTOR<\/jats:italic>,<jats:italic>p21<\/jats:italic>,<jats:italic>caspase-3<\/jats:italic>,<jats:italic>ULK1<\/jats:italic>,<jats:italic>TNF<jats:italic>\u03b1<\/jats:italic>, matrix metalloproteinase<\/jats:italic>(<jats:italic>MMP)-9<\/jats:italic>, and<jats:italic>cathepsin K<\/jats:italic>in the whole blood of rheumatoid arthritic (RA) patients treated with methotrexate (MTX) in relation to their rheumatoid factor status, clinical, immunological, and radiological parameters, and therapeutic response after a 24-month follow-up. The study group consisted of 35 control subjects and 33 RA patients without previous history of MTX treatment. Gene expression was measured using real-time RT-PCR. Decreased disease activity in patients at the end of the study was associated with significant downregulation of<jats:italic>TNF<jats:italic>\u03b1<\/jats:italic><\/jats:italic>expression. Downregulation of<jats:italic>mTOR<\/jats:italic>was observed in seronegative patients, while no significant changes in the expression of<jats:italic>p21<\/jats:italic>,<jats:italic>ULK1<\/jats:italic>, or<jats:italic>caspase-3<\/jats:italic>were noted in any RA patients at the end of the study. The increase in erosion numbers observed in the seropositive patients at the end of the follow-up was accompanied by upregulation of<jats:italic>MMP-9<\/jats:italic>and<jats:italic>cathepsin K<\/jats:italic>, while seronegative patients demonstrated an absence of significant changes in<jats:italic>MMP-9<\/jats:italic>and<jats:italic>cathepsin K<\/jats:italic>expression and no increase in the erosion score. Our results suggest that increased expression of<jats:italic>MMP-9<\/jats:italic>and<jats:italic>cathepsin K<\/jats:italic>genes in the peripheral blood might indicate higher bone tissue destruction activity in RA patients treated with methotrexate. The clinical study registration number is 0120.0810610.<\/jats:p>","DOI":"10.1155\/2013\/457876","type":"journal-article","created":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T16:15:18Z","timestamp":1384445718000},"page":"1-10","source":"Crossref","is-referenced-by-count":15,"title":["Rheumatoid Factor Positivity Is Associated with Increased Joint Destruction and Upregulation of<i>Matrix Metalloproteinase 9<\/i>and<i>Cathepsin K<\/i>Gene Expression in the Peripheral Blood in Rheumatoid Arthritic Patients Treated with Methotrexate"],"prefix":"10.1155","volume":"2013","author":[{"given":"Elena V.","family":"Tchetina","sequence":"first","affiliation":[{"name":"Clinical Immunology Department, Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences, Kashirskoye Shosse 34A, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia V.","family":"Demidova","sequence":"additional","affiliation":[{"name":"Early Rheumatoid 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