{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:58:08Z","timestamp":1777503488723,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2014,5,28]],"date-time":"2014-05-28T00:00:00Z","timestamp":1401235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Portuguese Science and Technology Foundation (FCT)","award":["PTDC\/SAU-ORG\/117266\/2010"],"award-info":[{"award-number":["PTDC\/SAU-ORG\/117266\/2010"]}]},{"name":"Portuguese Science and Technology Foundation (FCT)","award":["PTDC\/SAU-ORG\/112832\/2009"],"award-info":[{"award-number":["PTDC\/SAU-ORG\/112832\/2009"]}]},{"name":"CCMAR","award":["PEst-C\/MAR\/LA0015\/2011"],"award-info":[{"award-number":["PEst-C\/MAR\/LA0015\/2011"]}]},{"name":"Portuguese Science and Technology Foundation (FCT)","award":["PTDC\/SAU-ESA\/101186\/2008"],"award-info":[{"award-number":["PTDC\/SAU-ESA\/101186\/2008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>Gla\u2010rich protein (<jats:styled-content style=\"fixed-case\">GRP<\/jats:styled-content>) is a vitamin <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content> dependent protein, characterized by a high density of \u03b3\u2010carboxylated <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>lu residues, shown to accumulate in mouse and sturgeon cartilage and at sites of skin and vascular calcification in humans. Therefore, we investigated the involvement of <jats:styled-content style=\"fixed-case\">GRP<\/jats:styled-content> in pathological calcification in osteoarthritis (<jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Comparative analysis of <jats:styled-content style=\"fixed-case\">GRP<\/jats:styled-content> patterning at transcriptional and translational levels was performed between controls and <jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content> patients. Using a RT\u2010PCR strategy we unveiled two novel splice variants in human\u2014<jats:styled-content style=\"fixed-case\">GRP<\/jats:styled-content>\u2010F5 and F6\u2014potentially characterized by the loss of full \u03b3\u2010carboxylation and secretion functional motifs. <jats:styled-content style=\"fixed-case\">GRP<\/jats:styled-content>\u2010F1 is shown to be the predominant splice variant expressed in mouse and human adult tissues, particularly in <jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content> cartilage, while an overexpressing human cell model points it as the major \u03b3\u2010carboxylated isoform. Using validated conformational antibodies detecting carboxylated or undercarboxylated <jats:styled-content style=\"fixed-case\">GRP<\/jats:styled-content> (c\/uc <jats:styled-content style=\"fixed-case\">GRP<\/jats:styled-content>), we have demonstrated c<jats:styled-content style=\"fixed-case\">GRP<\/jats:styled-content> accumulation in controls, whereas uc<jats:styled-content style=\"fixed-case\">GRP<\/jats:styled-content> was the predominant form in <jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content>\u2010affected tissues, colocalizing at sites of ectopic calcification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Overall, our results indicate the predominance of <jats:styled-content style=\"fixed-case\">GRP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>1, and a clear association of uc<jats:styled-content style=\"fixed-case\">GRP<\/jats:styled-content> with <jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content> cartilage and synovial membrane. Levels of vitamin <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content> should be further assessed in these patients to determine its potential therapeutic use as a supplement in <jats:styled-content style=\"fixed-case\">OA<\/jats:styled-content> treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.201300941","type":"journal-article","created":{"date-parts":[[2014,5,28]],"date-time":"2014-05-28T08:07:01Z","timestamp":1401264421000},"page":"1636-1646","source":"Crossref","is-referenced-by-count":42,"title":["Insights into the association of <scp>G<\/scp>la\u2010rich protein and osteoarthritis, novel splice variants and \u03b3\u2010carboxylation status"],"prefix":"10.1002","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5518-9790","authenticated-orcid":false,"given":"Marta S.","family":"Rafael","sequence":"first","affiliation":[{"name":"Centre of Marine Sciences (CCMAR) University of Algarve  Faro Portugal"}]},{"given":"Sofia","family":"Cavaco","sequence":"additional","affiliation":[{"name":"Centre of Marine Sciences (CCMAR) University of Algarve  Faro Portugal"}]},{"given":"Carla S. 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