Estrogen-mediated miRNA101-3p expression represses HAS2 in synovial fibroblasts from idiopathic condylar resorption patients

Publication date: Available online 25 February 2019

Source: Journal of Oral and Maxillofacial Surgery

Author(s): Chi Feng, Ping Ji, Ping Luo, Jie Xu

Abstract

Purpose

Idiopathic condylar resorption (ICR) is an aggressive form of osteoarthritis that is frequently observed in adolescent females. We hypothesize that an estrogen-mediated pathway may contribute to ICR development.

Methods

Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of estradiol (E2) and hyaluronan (HA) in synovial fluid. Immunohistochemistry, real-time polymerase chain reaction (PCR), and western blotting were used to detect the expression of miRNAs and related genes after transfecting miRNA101-3p mimics, inhibitor, or siRNA into synovial fibroblasts. Dual luciferase activity was determined to identify the direct effect of miRNA101-3p on HAS2. Linear regression analysis, nonparametric Mann–Whitney U test, Student's t-test, and one-way analysis of variance were carried out to analyze the results of each group.

Results

The relationship between HA and E2 was negatively correlated in synovial fluid (Pearson r=-0.3179, p=0.0230). Among the screened miRNAs, miRNA101-3p was the most overexpressed in ICR. E2 mostly upregulated the expression of miRNA101-3p at a dose of 10 nM 12 h after transfection in synovial fibroblasts of patients with ICR. However, E2 induction of miRNA101-3p expression was significantly repressed by ERα interference. The dual luciferase assay demonstrated that miRNA101-3p regulated the expression of HAS2 by directly targeting its 3' UTR.

Conclusions

We speculate that E2 regulates HAS2 expression by targeting miRNA101-3p in synovial fibroblasts of patients with ICR. Thus, the E2/miRNA101-3p/HAS2 pathway might play an important role in the pathogenesis of ICR.

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