PT  - JOURNAL ARTICLE
AU  - Arijita Sarkar
AU  - Siyoung Lee
AU  - Ruzanna Shkhyan
AU  - Nancy Q. Liu
AU  - Ben Van Handel
AU  - Jenny Magallanes
AU  - Youngjoo Lee
AU  - Litao Tao
AU  - Neil Segil
AU  - Jason Ernst
AU  - Steve Horvath
AU  - Denis Evseenko
TI  - Genome-wide DNA methylation and multi-omics study of human chondrocyte ontogeny and an epigenetic clock analysis of adult chondrocytes
AID  - 10.1101/2021.08.02.454544
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.08.02.454544
4099  - http://biorxiv.org/content/early/2021/08/02/2021.08.02.454544.short
4100  - http://biorxiv.org/content/early/2021/08/02/2021.08.02.454544.full
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.