Altered MicroRNA Profile in Osteoporosis Caused by Impaired WNT Signaling

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http://hdl.handle.net/10138/311868

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Mäkitie , R E , Hackl , M , Niinimäki , R , Kakko , S , Grillari , J & Mäkitie , O 2018 , ' Altered MicroRNA Profile in Osteoporosis Caused by Impaired WNT Signaling ' , Journal of Clinical Endocrinology and Metabolism , vol. 103 , no. 5 , pp. 1985-1996 . https://doi.org/10.1210/jc.2017-02585

Title: Altered MicroRNA Profile in Osteoporosis Caused by Impaired WNT Signaling
Author: Mäkitie, Riikka E.; Hackl, Matthias; Niinimäki, Riitta; Kakko, Sakari; Grillari, Johannes; Mäkitie, Outi
Contributor: University of Helsinki, University of Helsinki
University of Helsinki, Clinicum
Date: 2018-05
Language: eng
Number of pages: 12
Belongs to series: Journal of Clinical Endocrinology and Metabolism
ISSN: 0021-972X
URI: http://hdl.handle.net/10138/311868
Abstract: Context: WNT signaling is fundamental to bone health, and its aberrant activation leads to skeletal pathologies. The heterozygous missense mutation p.C218G in WNT1, a key WNT pathway ligand, leads to severe early-onset and progressive osteoporosis with multiple peripheral and spinal fractures. Despite the severe skeletal manifestations, conventional bone turnover markers are normal in mutation-positive patients. Objective: This study sought to explore the circulating microRNA (miRNA) pattern in patients with impaired WNT signaling. Design and Setting: A cross-sectional cohort study at a university hospital. Participants: Altogether, 12 mutation-positive (MP) subjects (median age, 39 years; range, 11 to 76 years) and 12 mutation-negative (MN) subjects (35 years; range, 9 to 59 years) from two Finnish families with WNT1 osteoporosis due to the heterozygous p.C218G WNT1 mutation. Methods and Main Outcome Measure: Serum samples were screened for 192 miRNAs using quantitative polymerase chain reaction. Findings were compared between WNT1 MP and MN subjects. Results: The pattern of circulating miRNAs was significantly different in the MP subjects compared with the MN subjects, with two upregulated (miR-18a-3p and miR-223-3p) and six downregulated miRNAs (miR-22-3p, miR-31-5p, miR-34a-5p, miR-143-5p, miR-423-5p, and miR-423-3p). Three of these (miR-22-3p, miR-34a-5p, and miR-31-5p) are known inhibitors of WNT signaling: miR-22-3p and miR-34a-5p target WNT1 messenger RNA, and miR-31-5p is predicted to bind to WNT1 3'UTR. Conclusions: The circulating miRNA pattern reflects WNT1 mutation status. The findings suggest that the WNT1 mutation disrupts feedback regulation between these miRNAs and WNT1, providing insights into the pathogenesis of WNT-related bone disorders. These miRNAs may have potential in the diagnosis and treatment of osteoporosis.
Subject: MESENCHYMAL STEM-CELLS
PROMOTES OSTEOBLAST DIFFERENTIATION
OSTEOGENIC DIFFERENTIATION
BONE-FORMATION
POSTMENOPAUSAL OSTEOPOROSIS
OSTEOCLAST DIFFERENTIATION
WOMEN
EXPRESSION
FRACTURES
PATHWAY
3121 General medicine, internal medicine and other clinical medicine
3111 Biomedicine
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