{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:23:55Z","timestamp":1790504635502,"version":"4.1.0"},"reference-count":88,"publisher":"The Royal Society","issue":"1759","license":[{"start":{"date-parts":[[2018,9,24]],"date-time":"2018-09-24T00:00:00Z","timestamp":1537747200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Dynamic Cell PhD programme"],"award-info":[{"award-number":["Dynamic Cell PhD programme"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/L002566\/1"],"award-info":[{"award-number":["MR\/L002566\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","award":["21211 and 19476"],"award-info":[{"award-number":["21211 and 19476"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Phil. Trans. R. Soc. B"],"published-print":{"date-parts":[[2018,11,5]]},"abstract":"<jats:p>\n                    Collagen is the major structural component of cartilage, and mutations in the genes encoding type XI collagen are associated with severe skeletal dysplasias (fibrochondrogenesis and Stickler syndrome) and early-onset osteoarthritis (OA). The impact of the lack of type XI collagen on cell behaviour and mechanical performance during skeleton development is unknown. We studied a zebrafish mutant for\n                    <jats:italic>col11a2<\/jats:italic>\n                    and evaluated cartilage, bone development and mechanical properties to address this. We show that in\n                    <jats:italic>col11a2<\/jats:italic>\n                    mutants, type II collagen is made but is prematurely degraded in maturing cartilage and ectopically expressed in the joint. These changes are correlated with increased stiffness of both bone and cartilage; quantified using atomic force microscopy. In the mutants, the skeletal rudiment terminal region in the jaw joint is broader and the interzone smaller. These differences in shape and material properties impact on joint function and mechanical performance, which we modelled using finite element analyses. Finally, we show that\n                    <jats:italic>col11a2<\/jats:italic>\n                    heterozygous carriers reach adulthood but show signs of severe early-onset OA. Taken together, our data demonstrate a key role for type XI collagen in maintaining the properties of cartilage matrix; which when lost leads to alterations to cell behaviour that give rise to joint pathologies.\n                  <\/jats:p>\n                  <jats:p>This article is part of the Theo Murphy meeting issue \u2018Mechanics of development\u2019.<\/jats:p>","DOI":"10.1098\/rstb.2017.0335","type":"journal-article","created":{"date-parts":[[2018,9,24]],"date-time":"2018-09-24T03:25:56Z","timestamp":1537759556000},"page":"20170335","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":54,"title":["The mechanical impact of\n                    <i>col11a2<\/i>\n                    loss on joints;\n                    <i>col11a2<\/i>\n                    mutant zebrafish show changes to joint development and function, which leads to early-onset osteoarthritis"],"prefix":"10.1098","volume":"373","author":[{"given":"Elizabeth A.","family":"Lawrence","sequence":"first","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0266-9424","authenticated-orcid":false,"given":"Erika","family":"Kague","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9765-3758","authenticated-orcid":false,"given":"Jessye A.","family":"Aggleton","sequence":"additional","affiliation":[{"name":"School of Anthropology and Archaeology, University of Bristol, Bristol BS8 1UU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Harniman","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of Bristol, Bristol BS8 1TS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen A.","family":"Roddy","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4935-6724","authenticated-orcid":false,"given":"Chrissy L.","family":"Hammond","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2018,9,24]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-196850040-00002"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.106.3.991"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.108.1.191"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/1941738109350438"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(79)80024-8"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0049-0172(91)90035-X"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/jdb3040158"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2010.03.012"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90493-X"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(98)70466-4"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.09.001"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115452"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34406"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.48.3.580"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2007.06.007"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2003.12.002"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11233"},{"key":"e_1_3_6_19_2","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1002\/jor.23731","article-title":"Collagen XI mutation lowers susceptibility to load-induced cartilage damage in mice","volume":"36","author":"Holyoak DT","year":"2017","journal-title":"J. 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