{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:46:34Z","timestamp":1790844394874,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T00:00:00Z","timestamp":1492992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["STO 824\/3\u20101"],"award-info":[{"award-number":["STO 824\/3\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Cartilage damage and subchondral bone changes are closely connected in osteoarthritis. Nevertheless, how these processes are interlinked is, to date, incompletely understood. This study was undertaken to investigate the mechanistic role of a cartilage\u2010derived protein, upper zone of growth plate and cartilage matrix\u2013associated protein (UCMA), in osteoarthritis\u2010related cartilage and bone changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>UCMA expression was assessed in healthy and osteoarthritic human and mouse cartilage. For analysis of cartilage and bone changes, osteoarthritis was induced by destabilization of the medial meniscus (DMM) in wild\u2010type (WT) and <jats:italic>Ucma<\/jats:italic>\u2010deficient mice. UCMA\u2013collagen interactions, the effect of UCMA on aggrecanase activity, and the impact of recombinant UCMA on osteoclast differentiation were studied in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>UCMA was found to be overexpressed in human and mouse osteoarthritic cartilage. DMM\u2010triggered cartilage changes, including increased structural damage, proteoglycan loss, and chondrocyte cell death, were aggravated in <jats:italic>Ucma<\/jats:italic>\u2010deficient mice compared to WT littermates, thereby demonstrating the potential chondroprotective effects of UCMA. Moreover, UCMA inhibited ADAMTS\u2010dependent aggrecanase activity and directly interacted with cartilage\u2010specific collagen types. In contrast, osteoarthritis\u2010related bone changes were significantly reduced in <jats:italic>Ucma<\/jats:italic>\u2010deficient mice, showing less pronounced osteophyte formation and subchondral bone sclerosis. Mechanistically, UCMA directly promoted osteoclast differentiation in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>UCMA appears to link cartilage with bone changes in osteoarthritis by supporting cartilage integrity as an endogenous inhibitor of aggrecanases while also promoting osteoclastogenesis and subchondral bone turnover. Thus, UCMA represents an important link between cartilage and bone in osteoarthritis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40042","type":"journal-article","created":{"date-parts":[[2017,1,13]],"date-time":"2017-01-13T18:10:12Z","timestamp":1484331012000},"page":"1233-1245","source":"Crossref","is-referenced-by-count":32,"title":["A Dual Role of Upper Zone of Growth Plate and Cartilage Matrix\u2013Associated Protein in Human and Mouse Osteoarthritic Cartilage: Inhibition of Aggrecanases and Promotion of Bone Turnover"],"prefix":"10.1002","volume":"69","author":[{"given":"Michael","family":"Stock","sequence":"first","affiliation":[{"name":"Friedrich Alexander University of Erlangen\u2013N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Menges","sequence":"additional","affiliation":[{"name":"Friedrich Alexander University of Erlangen\u2013N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Eitzinger","sequence":"additional","affiliation":[{"name":"Friedrich Alexander University of Erlangen\u2013N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ge\u00dflein","sequence":"additional","affiliation":[{"name":"Friedrich Alexander University of Erlangen\u2013N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renate","family":"Botschner","sequence":"additional","affiliation":[{"name":"Friedrich Alexander University of Erlangen\u2013N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Wormser","sequence":"additional","affiliation":[{"name":"Friedrich Alexander University of Erlangen\u2013N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfiya","family":"Distler","sequence":"additional","affiliation":[{"name":"Friedrich Alexander University of Erlangen\u2013N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Schl\u00f6tzer\u2010Schrehardt","sequence":"additional","affiliation":[{"name":"Friedrich Alexander University of Erlangen\u2013N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Dietel","sequence":"additional","affiliation":[{"name":"Friedrich Alexander University of Erlangen\u2013N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Distler","sequence":"additional","affiliation":[{"name":"Friedrich Alexander University of Erlangen\u2013N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Beyer","sequence":"additional","affiliation":[{"name":"Friedrich Alexander University of Erlangen\u2013N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kolja","family":"Gelse","sequence":"additional","affiliation":[{"name":"Friedrich Alexander University of Erlangen\u2013N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Engelke","sequence":"additional","affiliation":[{"name":"Friedrich Alexander University of Erlangen\u2013N\u00fcrnberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marije I.","family":"Koenders","sequence":"additional","affiliation":[{"name":"Radboud University Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Radboud University Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"von der Mark","sequence":"additional","affiliation":[{"name":"Friedrich Alexander University of Erlangen\u2013N\u00fcrnberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Schett","sequence":"additional","affiliation":[{"name":"Friedrich Alexander University of Erlangen\u2013N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,4,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2011.01.022"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2153"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/1549168041552964"},{"key":"e_1_2_7_5_1","first-page":"309","article-title":"Cell density of adult human femoral condylar articular cartilage: joints with normal and fibrillated surfaces","volume":"49","author":"Mitrovic D","year":"1983","journal-title":"Lab Invest"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199809)41:9<1632::AID-ART14>3.0.CO;2-A"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199802)41:2<284::AID-ART12>3.0.CO;2-T"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1756-185X.2011.01618.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60802-3"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2006.11.006"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0505"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20124"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.11.017"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702792200"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2007.07.004"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2011.07.002"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2015.02.019"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.05.025"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38054"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20885"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.048926"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.179"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-216671"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22290"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201300941"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2015.03.005"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0795-330"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.11.5070"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610994200"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.050981"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2006.06.012"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4133"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.130"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2005.03.008"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2005.07.012"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.2002.2006"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI867"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2004.09.011"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80214-2"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2015.03.035"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M802761200"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.8.8954"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(01)00657-3"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.40042","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.40042","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.40042","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.40042","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T13:34:51Z","timestamp":1759930491000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.40042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,24]]},"references-count":42,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["10.1002\/art.40042"],"URL":"https:\/\/doi.org\/10.1002\/art.40042","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,24]]}}}