University of Oulu

Loid, P., Hauta-alus, H., Mäkitie, O., Magnusson, P., & Mäkitie, R. E. (2022). Lipocalin-2 is associated with FGF23 in WNT1 and PLS3 osteoporosis. Frontiers in Endocrinology, 13, 954730.

Lipocalin-2 is associated with FGF23 in WNT1 and PLS3 osteoporosis

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Author: Loid, Petra1,2,3; Hauta-alus, Helena2,3,4,5; Mäkitie, Outi1,2,3,6;
Organizations: 1Folkhälsan Research Center, Genetics Research Program, Helsinki, Finland
2Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
3University of Helsinki, Helsinki, Finland
4Population Health Unit, Finnish Institute for Health and Welfare (THL), Helsinki, Finland
5Research Unit for Pediatrics, Pediatric Neurology, Pediatric Surgery, Child Psychiatry, Dermatology, Clinical Genetics, Obstetrics and Gynecology, Otorhinolaryngology and Ophthalmology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
6Department of Molecular Medicine and Surgery, Karolinska Institutet, and Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
7Department of Clinical Chemistry, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
8Department of Otorhinolaryngology–Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.5 MB)
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Language: English
Published: Frontiers Media, 2022
Publish Date: 2023-01-26


Background: The pathogenic mechanisms of early-onset osteoporosis caused by WNT1 and PLS3 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.

Objective: 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.

Methods: We measured plasma lipocalin-2 in 17 WNT1 and 14 PLS3 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).

Results: 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 (r=0.62; p=0.008) and PLS3 patients (r=0.63, p=0.017), and with intact FGF23 in PLS3 patients (r=0.80; p<0.001). In addition, lipocalin-2 correlated with serum transferrin in WNT1 patients (r=0.72; p=0.001).

Conclusion: We conclude that plasma lipocalin-2 is not altered in WNT1 or PLS3 mutation-positive subjects but is associated with FGF23 in abnormal WNT1 or PLS3 signaling and with iron status in abnormal WNT1 signaling.

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Series: Frontiers in endocrinology
ISSN: 1664-2392
ISSN-E: 1664-2392
ISSN-L: 1664-2392
Volume: 13
Article number: 954730
DOI: 10.3389/fendo.2022.954730
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This work was funded by University of Helsinki and Helsinki University Hospital through the Doctoral Programme in Clinical Research, the Finnish Medical Foundation, Päivikki and Sakari Sohlberg Foundation, Juho Vainio Foundation, Sigrid Juse´lius Foundation, Novo Nordisk Foundation, Folkhälsan Research Foundation, the Finnish–Norwegian Research Foundation, Orion Research Foundation, The Finnish ORL– HNS Foundation and ALF grants from Region Östergötland. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.
Copyright information: © 2022 Loid, Hauta-alus, Mäkitie, Magnusson and Mäkitie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.