Genome-Wide Differentially Methylated Region Analysis to Reveal Epigenetic Differences of Articular Cartilage in Kashin-Beck Disease and Osteoarthritis.

Yue Fan,Yue Fan,Jiaqiang Zhu,Yingang Zhang,Dalong Gao,Feng Zhang,Feng Zhang,Dalong Gao,Yan Wen,Yan Wen,Shiquan Sun,Xiong Guo,Xiong Guo,Lu Wang,Shiquan Sun

doi:10.3389/fcell.2021.636291

Abstract

Kashin–Beck disease (KBD) is a degenerative osteoarticular disorder, and displays the significant differences with osteoarthritis (OA) regarding the etiology and molecular changes in articular cartilage. However, the underlying dysfunctions of molecular mechanisms in KBD and OA remain unclear. Here, we primarily performed the various genome-wide differential methylation analyses to reveal the distinct differentially methylated regions (DMRs) in conjunction with corresponding differentially methylated genes (DMGs), and enriched functional pathways in KBD and OA. We identified a total of 131 DMRs in KBD vs. Control, and 58 DMRs in OA vs. Controls, and the results demonstrate that many interesting DMRs are linked to DMGs, such as SMOC2 and HOXD3, which are all key genes to regulate cartilage/skeletal physiologic and pathologic process, and are further enriched in skeletal system and limb-associated pathways. Our DMR analysis indicates that KBD-associated DMRs has higher proportion than OA-associated DMRs in gene body regions. KBD-associated DMGs were enriched in wounding and coagulation-related functional pathways that may be stimulated by trace elements. The identified molecular features provide novel clues for understanding the pathogenetic and therapeutic studies of both KBD and OA.

Highlights

Kashin–Beck disease (KBD) is an endemic and chronic osteoarthropathy, widely affects the population in certain areas of Russia, North Korea, and China (Stone, 2009)
KBD and OA share several common characteristics in manifestation and pathological of articular cartilage, extensive studies have shown the significant differences in the etiology and molecular mechanism (Schepman et al, 2011)
The degenerative changes in KBD first appear in the deep zone of the cartilage and starts early in children as young as 2- or 3-year-old, while OA is diagnosed as the age-related disease and frequently compounded by various risk factors and biological age-related changes, including high-impact sports (Saxon et al, 1999), cardiovascular disease (Visman et al, 2019), and diabetes (Piva et al, 2015), etc

Summary

INTRODUCTION

Kashin–Beck disease (KBD) is an endemic and chronic osteoarthropathy, widely affects the population in certain areas of Russia, North Korea, and China (Stone, 2009). DMR Analysis for KBD and OA osteoarthritis (OA) is a chronic and degenerative joint disease, and affects the population in the worldwide, over 250 million people are currently affected by OA (Mora et al, 2018). The degenerative changes in KBD first appear in the deep zone (approximately 30–40% of articular cartilage thickness) of the cartilage and starts early in children as young as 2- or 3-year-old, while OA is diagnosed as the age-related disease and frequently compounded by various risk factors and biological age-related changes, including high-impact sports (Saxon et al, 1999), cardiovascular disease (Visman et al, 2019), and diabetes (Piva et al, 2015), etc. We annotated the DMRs to the associated differentially methylated genes (DMGs) to examine the exact role of DNA methylation in gene expression, and further performed the enrichment analysis to uncover the distinct functional pathways in KBD and OA

MATERIALS AND METHODS

RESULTS

DISCUSSION

ETHICS STATEMENT