The Potential Role of Genetics, Environmental Factors, and Gut Dysbiosis in the Aberrant Non-Coding RNA Expression to Mediate Inflammation and Osteoclastogenic/Osteogenic Differentiation in Ankylosing Spondylitis.

Abstract

Ankylosing spondylitis (AS) or radiographic axial spondyloarthritis is a chronic immune-mediated rheumatic disorder characterized by the inflammation in the axial skeleton, peripheral joints, and soft tissues (enthesis, fascia, and ligament). In addition, the extra-skeletal complications including anterior uveitis, interstitial lung diseases and aortitis are found. The pathogenesis of AS implicates an intricate interaction among HLA (HLA-B27) and non-HLA loci [endoplasmic reticulum aminopeptidase 1 (ERAP1), and interleukin-23 receptor (IL23R), gut dysbiosis, immune plasticity, and numerous environmental factors (infections, heavy metals, stress, cigarette smoking, etc.) The latter multiple non-genetic factors may exert a powerful stress on epigenetic regulations. These epigenetic regulations of gene expression contain DNA methylation/demethylation, histone modifications and aberrant non-coding RNAs (ncRNAs) expression, leading to inflammation and immune dysfunctions. In the present review, we shall discuss these contributory factors that are involved in AS pathogenesis, especially the aberrant ncRNA expression and its effects on the proinflammatory cytokine productions (TNF-α, IL-17 and IL-23), T cell skewing to Th1/Th17, and osteoclastogenic/osteogenic differentiation. Finally, some potential investigatory approaches are raised for solving the puzzles in AS pathogenesis.

• Authors: Hsien-Tzung Liao, Chang-Youh Tsai, Chien-Chih Lai, Song-Chou Hsieh, Yi-Syuan Sun, Ko-Jen Li, Chieh-Yu Shen, Cheng-Han Wu, Cheng-Hsun Lu, Yu-Min Kuo, Tzu-Hao Li, Chung-Tei Chou, Chia-Li Yu
• Journal: Frontiers in cell and developmental biology (Front Cell Dev Biol) Vol. 9 Pg. 748063 ( 2021) ISSN: 2296-634X [Print] Switzerland
• PMID: 35127698 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2022 Liao, Tsai, Lai, Hsieh, Sun, Li, Shen, Wu, Lu, Kuo, Li, Chou and Yu.