{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:18:10Z","timestamp":1791987490965,"version":"4.4.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T00:00:00Z","timestamp":1662595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007797","name":"Helsingin Yliopisto","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007797","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008376","name":"Helsingin ja Uudenmaan Sairaanhoitopiiri","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008376","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008723","name":"Suomen L\u00e4\u00e4ketieteen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008723","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004212","name":"P\u00e4ivikki ja Sakari Sohlbergin S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004212","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004037","name":"Juho Vainion S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004037","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015736","name":"Folkh\u00e4lsanin Tutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015736","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019841","name":"Suomalais-Norjalainen L\u00e4\u00e4ketieteen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019841","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007083","name":"Orionin Tutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007083","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018862","name":"Korvatautien Tutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018862","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016670","name":"Region \u00d6sterg\u00f6tland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016670","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The pathogenic mechanisms of early-onset osteoporosis caused by <jats:italic>WNT1<\/jats:italic> and <jats:italic>PLS3<\/jats:italic> mutations are incompletely understood and diagnostic biomarkers of these disorders are limited. Recently, lipocalin-2 has been recognized as an osteokine involved in bone development and homeostasis. However, the role of lipocalin-2 in WNT1 and PLS3 osteoporosis is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We aimed to investigate if plasma lipocalin-2 could be utilized as a biomarker for WNT1 and PLS3 osteoporosis and to evaluate the association between lipocalin-2 and other parameters of bone metabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We measured plasma lipocalin-2 in 17 <jats:italic>WNT1<\/jats:italic> and 14 <jats:italic>PLS3<\/jats:italic> mutation-positive patients and compared them to those of 34 mutation-negative (MN) healthy subjects. We investigated possible associations between lipocalin-2 and several bone biomarkers including collagen type I cross-linked C-telopeptide (CTX), alkaline phosphatase (ALP), type I procollagen intact N-terminal propeptide (PINP), intact and C-terminal fibroblast growth factor 23 (FGF23), dickkopf-1 (DKK1) and sclerostin as well as parameters of iron metabolism (iron, transferrin, transferrin saturation, soluble transferrin receptor and ferritin).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found no differences in plasma lipocalin-2 levels in WNT1 or PLS3 patients compared with MN subjects. However, lipocalin-2 was associated with C-terminal FGF23 in WNT1 patients (<jats:italic>r<\/jats:italic>=0.62; <jats:italic>p=<\/jats:italic>0.008) and PLS3 patients (r=0.63, p=0.017), and with intact FGF23 in PLS3 patients (<jats:italic>r<\/jats:italic>=0.80; <jats:italic>p<\/jats:italic>&amp;lt;0.001). In addition, lipocalin-2 correlated with serum transferrin in WNT1 patients (<jats:italic>r<\/jats:italic>=0.72; <jats:italic>p<\/jats:italic>=0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We conclude that plasma lipocalin-2 is not altered in <jats:italic>WNT1<\/jats:italic> or <jats:italic>PLS3<\/jats:italic> mutation-positive subjects but is associated with FGF23 in abnormal WNT1 or PLS3 signaling and with iron status in abnormal WNT1 signaling.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.954730","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T10:47:19Z","timestamp":1662634039000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Lipocalin-2 is associated with FGF23 in WNT1 and PLS3 osteoporosis"],"prefix":"10.3389","volume":"13","author":[{"given":"Petra","family":"Loid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Hauta-alus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Outi","family":"M\u00e4kitie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Magnusson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riikka E.","family":"M\u00e4kitie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1215458","article-title":"WNT1 mutations in early-onset osteoporosis and osteogenesis 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