Mäkitie RE, et al. - Experts assessed the circulating microRNA (miRNA) pattern in osteoporosis patients with impaired WNT signaling in a cross-sectional cohort study at a university hospital. WNT1 mutation status is reflected by the circulating miRNA pattern. Feedback regulation between these miRNAs and WNT1 was seen to be disrupted by the WNT1 mutation, thereby providing insights into the pathogenesis of WNT-related bone disorders. These miRNAs may provide success in the diagnosis and treatment of osteoporosis.

Methods

• In this cross-sectional cohort study at a university hospital, 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) were included from two Finnish families with WNT1 osteoporosis due to the heterozygous p.C218G WNT1 mutation.
• Serum samples were screened for 192 miRNAs using quantitative polymerase chain reaction, and then the authors compared the findings between WNT1 MP and MN subjects.

Results

• As per data, a significant difference in the pattern of circulating miRNAs was seen in the MP subjects vs 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).
• Findings suggested that 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.