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

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

doi:10.3389/fcell.2021.636291

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

Front Cell Dev Biol. 2021 Mar 1:9:636291. doi: 10.3389/fcell.2021.636291. eCollection 2021.

Authors

Yue Fan^{1

2}, Dalong Gao^{3

4}, Yingang Zhang⁵, Jiaqiang Zhu⁶, Feng Zhang^{1

2}, Lu Wang⁷, Yan Wen^{1

2}, Xiong Guo^{1

2}, Shiquan Sun^{1

2}

Affiliations

¹ School of Public Health, Health Science Center of Xi'an Jiaotong University, Xi'an, China.
² Key Laboratory of Trace Elements and Endemic Diseases of National Health Commission and Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk Road Region, Xi'an, China.
³ Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
⁴ Department of Orthopaedics, The Central Hospital of Xianyang, Xianyang, China.
⁵ Department of Orthopaedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
⁶ Department of Biostatistics, University of Michigan, Ann Arbor, MI, United States.
⁷ Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.

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.

Keywords: DNA methylation; Kashin–Beck disease; articular cartilage; cartilage; differentially methylated region; osteoarthritis.