Estrogen-Mediated MicroRNA-101-3p Expression Represses Hyaluronan Synthase 2 in Synovial Fibroblasts From Idiopathic Condylar Resorption Patients.

Purpose: Idiopathic condylar resorption (ICR) is an aggressive form of osteoarthritis that is frequently observed in adolescent female patients. We hypothesized that an estrogen-mediated pathway may contribute to ICR development.

Materials And Methods: An enzyme-linked immunosorbent assay was used to detect the levels of estradiol (E2) and hyaluronan in synovial fluid. Immunohistochemistry, real-time polymerase chain reaction, and Western blotting were used to detect the expression of microRNAs (miRNAs) and related genes after transfection of miRNA-101-3p mimics, inhibitor, or short interfering RNA into synovial fibroblasts. Dual-luciferase activity was determined to identify the direct effect of miRNA-101-3p on hyaluronan synthase 2 (HAS2). Linear regression analysis, the nonparametric Mann-Whitney U test, the Student t test, and 1-way analysis of variance were carried out to analyze the results of each group.

Results: The relationship between hyaluronan and E2 was negatively correlated in synovial fluid (Pearson r = -0.3179, P = .0230). Among the screened miRNAs, miRNA-101-3p was the most overexpressed in ICR. E2 mostly upregulated the expression of miRNA-101-3p at a dose of 10 nmol/L 12 hours after transfection in synovial fibroblasts of patients with ICR. However, E2 induction of miRNA-101-3p expression was significantly repressed by estrogen receptor α interference (P = 0.0286). The dual-luciferase assay showed that miRNA-101-3p regulated the expression of HAS2 by directly targeting its 3' untranslated region.

Conclusions: We speculate that E2 regulates HAS2 expression by targeting miRNA-101-3p in synovial fibroblasts of patients with ICR. Thus, the E2-miRNA-101-3p-HAS2 pathway might play an important role in the pathogenesis of ICR.