RT Journal Article
SR Electronic
T1 Genome-wide DNA methylation and multi-omics study of human chondrocyte ontogeny and an epigenetic clock analysis of adult chondrocytes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.02.454544
DO 10.1101/2021.08.02.454544
A1 Arijita Sarkar
A1 Siyoung Lee
A1 Ruzanna Shkhyan
A1 Nancy Q. Liu
A1 Ben Van Handel
A1 Jenny Magallanes
A1 Youngjoo Lee
A1 Litao Tao
A1 Neil Segil
A1 Jason Ernst
A1 Steve Horvath
A1 Denis Evseenko
YR 2021
UL http://biorxiv.org/content/early/2021/08/02/2021.08.02.454544.abstract
AB Articular chondrocytes undergo functional changes and their regenerative potential declines with age. Although the molecular mechanisms guiding articular cartilage aging is poorly understood, DNA methylation is known to play a mechanistic role in aging. However, our understanding of DNA methylation in chondrocyte development across human ontogeny is limited. To better understand DNA methylome changes, methylation profiling was performed in human chondrocytes. This study reveals association between methylation of specific CpG sites and chondrocyte age. We also determined the putative binding targets of STAT3, a key age-patterned transcription factor in fetal chondrocytes and genetic ablation of STAT3 induced a global genomic hypermethylation. Moreover, an epigenetic clock built for adult human chondrocytes revealed that exposure of aged adult human chondrocytes to STAT3 agonist, decreased epigenetic age. Taken together, this work will serve as a foundation to understand development and aging of chondrocytes with a new perspective for development of rejuvenation agents for synovial joints.Competing Interest StatementThe authors have declared no competing interest.