Histone methylation as a marker of chondrocyte phenotype

Abstract

Maintaining articular chondrocyte phenotype is important in terms of pathological conditions and cartilage development, but is complicated and challenging. Epigenetic modifications are one kind of those factors which have effect on cell phenotype regulation. However, the extent to which epigenetics marks in forms of trimethylation of histone H3 Lysine 4 and 27 (H3K4me3 and H3K27me3) regulate chondrocytes phenotype and characteristic gene expression remains largely unknown. In this study, we studied H3K4me3 and H3K27me3 level in the Sox9 promoter in human articular chondrocytes (hACs) comparing human adipose-derived mesenchymal stem cells (hASCs), and global H3K4me3 level in hACs comparing dedifferentiated hACs. Our ChIP-qPCR data showed largely lower H3K27me3 in the Sox9 promoter in hACs than in hASCs, suggesting that repressive chromatin in the Sox9 promoter decreases in the chondrocyte phenotype. Western blotting data showed higher H3K4me3 level in hACs during dedifferentiation. In summary, our results suggest that these epigenetic marks may regulate chondrocyte phenotype, and could be used as unique marks distinguish the hACs phenotype from other lineages and change during dedifferentiation.