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Histone Modifications and Chondrocyte Fate: Regulation and Therapeutic Implications

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

Journal

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY

Volume 9, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA

DOI: 10.3389/fcell.2021.626708

Keywords

epigenetics; histone modification; chondrocyte; articular cartilage; regeneration; osteoarthritis

Funding

Hong Kong SAR Research Grant Council General Research Fund [14121815, 14174617]
Shenzhen Virtue University Park Laboratory Support Special Fund [YFJGJS1.0]
Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing, China
Lee Quo Wei and Lee Yick Hoi Lun Professorship in Tissue Engineering and Regenerative Medicine

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Abstract

Histone modifications play a significant role in cartilage development, pathology, and regeneration. Targeting histone modifying proteins with candidate molecules or drugs shows promising therapeutic potential in treating cartilage lesions associated with joint degeneration.

The involvement of histone modifications in cartilage development, pathology and regeneration is becoming increasingly evident. Understanding the molecular mechanisms and consequences of histone modification enzymes in cartilage development, homeostasis and pathology provides fundamental and precise perspectives to interpret the biological behavior of chondrocytes during skeletal development and the pathogenesis of various cartilage related diseases. Candidate molecules or drugs that target histone modifying proteins have shown promising therapeutic potential in the treatment of cartilage lesions associated with joint degeneration and other chondropathies. In this review, we summarized the advances in the understanding of histone modifications in the regulation of chondrocyte fate, cartilage development and pathology, particularly the molecular writers, erasers and readers involved. In addition, we have highlighted recent studies on the use of small molecules and drugs to manipulate histone signals to regulate chondrocyte functions or treat cartilage lesions, in particular osteoarthritis (OA), and discussed their potential therapeutic benefits and limitations in preventing articular cartilage degeneration or promoting its repair or regeneration.

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STAT3 promotes a youthful epigenetic state in articular chondrocytes

Arijita Sarkar, Nancy Q. Q. Liu, Jenny Magallanes, Jade Tassey, Siyoung Lee, Ruzanna Shkhyan, Youngjoo Lee, Jinxiu Lu, Yuxin Ouyang, Hanhan Tang, Fangzhou Bian, Litao Tao, Neil Segil, Jason Ernst, Karen Lyons, Steve Horvath, Denis Evseenko

Summary: This study establishes an epigenetic clock based on DNA methylation profiling of human chondrocytes and reveals an association between CpG methylation and chondrocyte age. It also demonstrates the role of STAT3 in regulating DNA methylation in chondrocyte development and osteoarthritis. Furthermore, functional assessment shows that a subset of chondrocytes acquire a progenitor-like phenotype.

AGING CELL (2023)