Growth plate-like H3K27me3 loss in bivalent genes promote OA (IMAGE)
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During the process of endochondral ossification in growth plate cartilage, hypertrophic genes are marked by both H3K27me3 and H3K4me3 to enable rapid activation when needed. In articular cartilage, which shares a common origin with growth plate cartilage, these hypertrophic genes remain in a bivalent state. Under physiological conditions, these genes are transcriptionally repressed. However, under pathological conditions of osteoarthritis (OA), the repressive mark H3K27me3 is lost, leading to the activation of hypertrophic genes, which promotes cartilage matrix degradation and contributes to OA progression.
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