Estrogen Affects HAS2 Expression In Synovial Fibroblasts From Idiopathic Condylar Resorption Patients Via MiRNA101-3p

Idiopathic condylar resorption(ICR)is an aggressive form of osteoarthritis with an unknown etiology.ICR and temporomandibular joint osteoarthritis(TMJOA)share both similarities and differences in clinical manifestation and pathogenesis.Unlike the slow destruction of fibrocartilage observed in osteoarthritis,ICR progresses rapidly until the whole condylar head is resorbed.Additionally,ICR has typical clinical and radiographic manifestations including an incidence between the age of 12 and 24 years,anterior open bite,facial deformity,destruction of the condylar cortex,and resorption of the condylar head.Presently,there is no effective early diagnosis or biologically based treatment for ICR.While the etiology is poorly understood,ICR risk factors include hormonal changes,parafunctional habits,trauma,internal joint derangement,and orthodontics.Because it often occurs in adolescent women,it is reasonable to investigate estrogen-based pathways that may lead to ICR pathogenesis.This study will explore the regulatory role of E2 in ICR.To provide a theoretical basis for the pathogenesis of ICR,and finally to help the clinical diagnosis and treatment of ICR.Materials and methods: Synovial fluid was collected from the superior synovial cavity of the joint.Synovial membranes were collected from patients undergoing joint surgery.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of 17?-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 mi RNAs and related genes after transfecting mi RNA101-3p mimics,inhibitor,or si RNA into synovial fibroblasts.Dual luciferase activity was determined to identify the direct effect of mi RNA 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).the ER expression in ICR synovial fibroblasts was approximately 2.1-fold higher than that in DD synovial fibroblasts at the protein level.Immunohistochemical staining revealed that the expression of ER was distributed in both the synovial lining layer and the sublining layer.Among the screened mi RNAs,mi RNA101-3p was the most overexpressed in ICR.E2 mostly upregulated the expression of mi RNA101-3p at a dose of 10 n M12 h after transfection in synovial fibroblasts of patients with ICR.However,E2 induction of mi RNA101-3p expression was significantly repressed by ER? interference.The dual luciferase assay demonstrated that mi RNA101-3p regulated the expression of HAS2 by directly targeting its3'-UTR.Conclusions: We speculate that E2 regulates HAS2 expression by targeting mi RNA101-3p in synovial fibroblasts of patients with ICR.Thus,the E2/mi RNA101-3p/HAS2 pathway might play an important role in the pathogenesis of ICR.