Fig. 8: Schematic illustration of how epigenetic changes affect cartilage ECM integrity. | Cell Death & Disease

Fig. 8: Schematic illustration of how epigenetic changes affect cartilage ECM integrity.

From: Histone H3K27 demethylase UTX compromises articular chondrocyte anabolism and aggravates osteoarthritic degeneration

Fig. 8

Age-dependent changes in articular chondrocytes that are leading to an increased UTX activity (i.e., mimicked by lentiviral overexpression) are, together with histone writer PRC2 core components EED and SUZ12, resulting in an elevated histone methylation state in these cells, consequently dysregulating cartilage homeostasis. Also, this epigenetic signature suppresses SOX9 activity, which is crucial for maintaining ECM integrity. Ultimately, this culminates in the development of OA. In contrast, inhibiting UTX facilitates transcriptional activity at promoter regions of certain cartilage key markers (like e.g., SOX9, Col2a1, ACAN) at least partially through co-suppression of Eed and Suz12. This net stimulation of anabolic factors then aids in maintaining the ECM integrity of the tissue to ensure proper homeostasis.

Back to article page