Folkhälsan Research Center, Genetics Research Program, Helsinki, Finland.
Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Front Endocrinol (Lausanne). 2022 Sep 8;13:954730. doi: 10.3389/fendo.2022.954730. eCollection 2022.
The pathogenic mechanisms of early-onset osteoporosis caused by and 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.
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.
We measured plasma lipocalin-2 in 17 and 14 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).
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 (=0.62; 0.008) and PLS3 patients (r=0.63, p=0.017), and with intact FGF23 in PLS3 patients (=0.80; <0.001). In addition, lipocalin-2 correlated with serum transferrin in WNT1 patients (=0.72; =0.001).
We conclude that plasma lipocalin-2 is not altered in or mutation-positive subjects but is associated with FGF23 in abnormal WNT1 or PLS3 signaling and with iron status in abnormal WNT1 signaling.
和突变引起的早发性骨质疏松症的发病机制尚不完全清楚，这些疾病的诊断生物标志物也很有限。最近，脂联素-2 已被认为是一种参与骨发育和稳态的骨细胞因子。然而，脂联素-2 在 WNT1 和 PLS3 骨质疏松症中的作用尚不清楚。
我们旨在研究血浆脂联素-2 是否可用作 WNT1 和 PLS3 骨质疏松症的生物标志物，并评估脂联素-2 与其他骨代谢参数之间的关系。
我们测量了 17 名和 14 名突变阳性患者的血浆脂联素-2，并将其与 34 名突变阴性（MN）健康受试者进行了比较。我们研究了脂联素-2 与几种骨生物标志物之间的可能关联，包括 I 型胶原交联 C 端肽（CTX）、碱性磷酸酶（ALP）、I 型前胶原完整 N 端前肽（PINP）、完整和 C 端成纤维细胞生长因子 23（FGF23）、Dickkopf-1（DKK1）和硬化蛋白以及铁代谢参数（铁、转铁蛋白、转铁蛋白饱和度、可溶性转铁蛋白受体和铁蛋白）。
我们发现 WNT1 或 PLS3 患者的血浆脂联素-2 水平与 MN 受试者相比没有差异。然而，脂联素-2 与 WNT1 患者的 C 端 FGF23 相关（r=0.62；0.008）和 PLS3 患者（r=0.63，p=0.017），与 PLS3 患者的完整 FGF23 相关（r=0.80；<0.001）。此外，脂联素-2 与 WNT1 患者的血清转铁蛋白相关（r=0.72；=0.001）。
我们得出结论，血浆脂联素-2 在或突变阳性患者中没有改变，但在异常的 WNT1 或 PLS3 信号传导中与 FGF23 相关，在异常的 WNT1 信号传导中与铁状态相关。
