Abstract
Ankylosing spondylitis (AS) is a chronic autoimmune disease characterized by systemic inflammation and pathological osteogenesis. However, the genetic etiology of AS remains largely unknown. This study aimed to explore the potential role of coding and noncoding genes in the genetic mechanism of AS. Using microarray analyses, this study comprehensively compared lncRNA, microRNA, and mRNA profiles in hip joint ligament tissues from patients with AS and controls. A total of 661 lncRNAs, 574 mRNAs, and 22 microRNAs were differentially expressed in patients with AS compared with controls. Twenty-two of these genes were then validated using real-time polymerase chain reaction. Gene ontology and pathway analyses were performed to explore the principal functions of differentially expressed genes. The pathways were involved mainly in immune regulation, intercellular signaling, osteogenic differentiation, protein synthesis, and degradation. Gene signal transduction network, coding–noncoding co-expression network, and competing endogenous RNA expression network were constructed using bioinformatics methods. Then, two miRNAs, miR-17-5p and miR-27b-3p, that could increase the osteogenic differentiation potentials of ligament fibroblasts were identified. Finally, differentially expressed, five lncRNAs, four miRNAs, and five mRNAs were validated using quantitative real-time polymerase chain reaction. These results suggested that mRNAs, lncRNAs, and microRNAs were involved in AS pathogenesis. The findings might help characterize the pathogenesis of AS and provide novel therapeutic targets for patients with AS in the future.
Highlights
Ankylosing spondylitis (AS) is a chronic autoimmune disease characterized by systemic inflammation and pathological osteogenesis [1]
Differentially expressed, five long noncoding RNA (lncRNA), four miRNAs, and five messenger RNA (mRNA) were validated using quantitative real-time polymerase chain reaction. These results suggested that mRNAs, lncRNAs, and microRNAs were involved in AS pathogenesis
A total of 661 lncRNAs, 574 mRNAs, and 22 miRNAs were found to be differentially expressed (DE) in the AS group compared with the control group
Summary
Ankylosing spondylitis (AS) is a chronic autoimmune disease characterized by systemic inflammation and pathological osteogenesis [1]. It initially involves the sacroiliac joints, and affects mainly the axial skeleton, tendon attachment points, and ligaments [2]. AS eventually leads to ligamentous ossifications and spinal fusion, which bring a great burden to patients and society. Several studies have explored the pathogenesis of inflammation in AS. The real cause of the disease is still unknown. The mechanism of new bone formation remains poorly understood. In-depth studies on the precise mechanisms of inflammation and new bone formation in AS should provide valuable information
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