Hyper-physiologic mechanical cues, as an osteoarthritis disease-relevant environmental perturbation, cause a critical shift in set points of methylation at transcriptionally active CpG sites in neo-cartilage organoids.

Notable examples of highly significant DM CpG sites are cg27310485 annotated to calcium binding protein S100A2 (beta = 0.01, FDR = 7.8X10 −4 ), cg16217885 annotated to inflammatory receptor IL1R1 (beta = 0.01, FDR = 1.2 × 10 –3 ), and cg12795959 annotated to SIRPB1 (beta = -0.03, FDR = 2.4 × 10 –7 ).

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Upon defining DMRs as 3 or more DM CpGs with an inter-CpG distance of < 1 kb and allowing for 3 non-DM CpGs in the complete DMR [ 16 ], these DMRs did not reach statistical significance.

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