MicroRNA-146a knockdown suppresses the progression of ankylosing spondylitis by targeting dickkopf 1

Abstract

Ankylosing spondylitis (AS) seriously threatens healthy and life quality of patients, however, there is no extremely effective drug to cure the disease. Therefore, it is urgent to understand molecular basis in the progression of AS. MicroRNA-146a (miR-146a) has been demonstrated to be associated with the development of AS. However, its molecular mechanism has not been fully established. In this study, it is found that the expression levels of miR-146a and dickkopf 1 (DKK1) were respectively upregulated and downregulated in hip capsule tissues of AS patients. Moreover, a negative correlation was displayed between miR-146a and DKK1 expression. Functional analysis revealed that miR-146a inhibitor restrained cell proliferation and osteogenic potential as well as enhanced apoptosis in AS fibroblasts, while miR-146a overexpression enhanced proliferation and osteogenic potential of AS fibroblasts. Bioinformatics analysis, dual luciferase reporter assays, qRT-PCR and immunoblotting assays revealed that miR-146a inhibited DKK1 expression by directly targeting 3’UTR region of DKK1. Mechanism studies further revealed that loss of DKK1 partly reversed the effect of miR-146a inhibitor on cell proliferation, apoptosis and osteogenic potential in AS fibroblasts. Taken together, our finding revealed that miR-146a knockdown hindered AS progression partially by regulating target DKK1 expression, offering a potential therapy application for AS patients.