Identification of DNA methylation changes associated with disease progression in subchondral bone with site-matched cartilage in knee osteoarthritis

Yanfei Zhang; Naoshi Fukui; Mitsunori Yahata; Yozo Katsuragawa; Toshiyuki Tashiro; Shiro Ikegawa; Ming Ta Michael Lee

doi:10.1038/srep34460

Identification of DNA methylation changes associated with disease progression in subchondral bone with site-matched cartilage in knee osteoarthritis

Sci Rep. 2016 Sep 30:6:34460. doi: 10.1038/srep34460.

Authors

Yanfei Zhang^{1

2}, Naoshi Fukui^{3

4}, Mitsunori Yahata^{1

5}, Yozo Katsuragawa⁶, Toshiyuki Tashiro⁷, Shiro Ikegawa⁸, Ming Ta Michael Lee^{1

2

9}

Affiliations

¹ Laboratory for International Alliance on Genomic Research, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
² Genomic Medicine Institute, Geisinger Health System, Danville, PA, USA.
³ Clinical Research Center, National Hospital Organization Sagamihara Hospital, Kanagawa, Japan.
⁴ Department of Life Sciences, Graduate School of Arts and Sciences, the University of Tokyo, Tokyo, Japan.
⁵ Laboratory for Pharmacogenomics, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
⁶ Department of Orthopaedic Surgery, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan.
⁷ Department of Orthopaedic Surgery, Tokyo Yamate Medical Center, Tokyo, Japan.
⁸ Laboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan.
⁹ Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

Abstract

Subchondral bone plays a key role in the development of osteoarthritis, however, epigenetics of subchondral bone has not been extensively studied. In this study, we examined the genome-wide DNA methylation profiles of subchondral bone from three regions on tibial plateau representing disease progression using HumanMethylation450 BeadChip to identify progression associated DNA methylation alterations. Significant differential methylated probes (DMPs) and differential methylated genes (DMGs) were identified in the intermediate and late stages and during the transition from intermediate to late stage of OA in the subchondral bone. Over half of the DMPs were hyper-methylated. Genes associated with OA and bone remodeling were identified. DMGs were enriched in morphogenesis and development of skeletal system, and HOX transcription factors. Comparison of DMGs identified in subchondral bone and site-matched cartilage indicated that DNA methylation changes occurred earlier in subchondral bone and identified different methylation patterns at the late stage of OA. However, shared DMPs, DMGs and common pathways that implicated the tissue reparation were also identified. Methylation is one key mechanism to regulate the crosstalk between cartilage and subchondral bone.