{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T23:54:34Z","timestamp":1784591674825,"version":"3.55.0"},"reference-count":55,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,9,22]],"date-time":"2017-09-22T00:00:00Z","timestamp":1506038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG007996"],"award-info":[{"award-number":["AG007996"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Deposition of amyloid is a common aging\u2010associated phenomenon in several aging\u2010related diseases. Osteoarthritis (<jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content>) is the most prevalent joint disease, and aging is its major risk factor. Transthyretin (<jats:styled-content style=\"fixed-case\">TTR<\/jats:styled-content>) is an amyloidogenic protein that is deposited in aging and <jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content>\u2010affected human cartilage and promotes inflammatory and catabolic responses in cultured chondrocytes. Here, we investigated the role of <jats:styled-content style=\"fixed-case\">TTR <\/jats:styled-content><jats:italic>in\u00a0vivo<\/jats:italic> using transgenic mice overexpressing wild\u2010type human <jats:italic><jats:styled-content style=\"fixed-case\">TTR<\/jats:styled-content><\/jats:italic> (<jats:styled-content style=\"fixed-case\">hTTR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>). Although <jats:styled-content style=\"fixed-case\">TTR<\/jats:styled-content> protein was detected in cartilage in <jats:styled-content style=\"fixed-case\">hTTR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content> mice, the <jats:italic><jats:styled-content style=\"fixed-case\">TTR<\/jats:styled-content><\/jats:italic> transgene was highly overexpressed in liver, but not in chondrocytes. OA was surgically induced by destabilizing the medial meniscus (<jats:styled-content style=\"fixed-case\">DMM<\/jats:styled-content>) in <jats:styled-content style=\"fixed-case\">hTTR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content> mice, wild\u2010type mice of the same strain (<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>), and mice lacking endogenous <jats:italic>Ttr<\/jats:italic> genes. In the <jats:styled-content style=\"fixed-case\">DMM<\/jats:styled-content> model, both cartilage and synovitis histological scores were significantly increased in <jats:styled-content style=\"fixed-case\">hTTR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content> mice. Further, spontaneous degradation and <jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content>\u2010like changes in cartilage and synovium developed in 18\u2010month\u2010old <jats:styled-content style=\"fixed-case\">hTTR<\/jats:styled-content> mice. Expression of cartilage catabolic <jats:italic>(Adamts4, Mmp13)<\/jats:italic> and inflammatory genes (<jats:italic>Nos2, Il6<\/jats:italic>) was significantly elevated in cartilage from 6\u2010month\u2010old <jats:styled-content style=\"fixed-case\">hTTR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content> mice compared with <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> mice as was the level of phospho\u2010<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB p65. Intra\u2010articular injection of aggregated <jats:styled-content style=\"fixed-case\">TTR<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> mice increased synovitis and significantly increased expression of inflammatory genes in synovium. These findings are the first to show that <jats:styled-content style=\"fixed-case\">TTR<\/jats:styled-content> deposition increases disease severity in the murine <jats:styled-content style=\"fixed-case\">DMM<\/jats:styled-content> and aging model of OA.<\/jats:p>","DOI":"10.1111\/acel.12665","type":"journal-article","created":{"date-parts":[[2017,9,23]],"date-time":"2017-09-23T04:08:45Z","timestamp":1506139725000},"page":"1313-1322","source":"Crossref","is-referenced-by-count":33,"title":["Transthyretin deposition promotes progression of osteoarthritis"],"prefix":"10.1111","volume":"16","author":[{"given":"Tokio","family":"Matsuzaki","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine The Scripps Research Institute La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Akasaki","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine The Scripps Research Institute La Jolla CA 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