Table 2: Genome-wide methylome and genome-wide 5-hydroxymethylome profiles in osteoarthritis.

Sample (n) CpG sites analyzed DML Gene Ontology Analysis a Ref.
All Hyper-methylated Hypo-methylated
THR and Osteoporotic hip
(26 vs. 27)
> 27,000 241 217 24 Homeobox superfamily of TF (HOXA9, IRX2, MSX2) and genes of cell differentiation [59]
TKR and Healthy controls b
(25 vs. 20)
> 27,000 91 54 37 Inflammation and Regulation of transcriptional activity-related genes and RUNX1 and MSX1 genes [60]
(23/73 vs 21)
>485,000 [61]
THR vs. #NOF 5,322 2,669 2,653 Degradation of ECM, anabolic/catabolic pathway of cartilage homeostasis, TGF-β pathway
THR Cluster1 vs. Cluster2c 15,239 8,524 6,915 Inflammation, Cartilage degradation, and TGF-β pathways
TKR Cluster1 vs. Cluster2c 5,769 3,000 2,769 Immune response
THR vs. TKR 5,547 2,598 2,949 Genes involved in OA pathogenesis (ADAM12, ADAMTS5, GDF5)
OA vs. Intact cartilage >485,000 550 172 378 TGF-β pathway genes and RUNX1 and FURIN
~244,000 1,214 1,070 144 TGF-β and WNT pathways [63]
Severe OA vs. Mild OA d Hypermethylation of genes related with TGF-β (BMP2, BMP4, MAPK3, SMAD)
TKR vs. THR 6,272 Developmental pathways (limb development and skeletal system morphogenesis) [64]
Damaged vs. Undamaged cartilage
(14 vs. 17)
Homeobox (HOX) cluster
TKR, THR, and controls
(5, 6, and 7)
>485,000 Skeletal and embryonic organ system development and Homeobox (HOX) [65]
TKR vs. Controls 72
THR vs. Controls 26
TKR/THR vs. Controls 103
THR vs. TKR 67
After removing overlaps 239 112 127
TKR vs. Ligament reconstruction
(4 vs. 4)
70,591e 44,288f 26,303g Increased DhMR in Wnt-signalling and bone-remodeling pathways [66]
Loss of DhMR in cell adhesion, skeletal muscle development
Gene expression change in MMpP3, MMP13 and inflammation-related genes

DML: Differential Methylated Loci; THR: Total Hip Replacement; TKR: Total Knee Replacement; NOF#: Neck of Femur fracture. a: The main results are presented b: Obtained at autopsy from cadavers with no macroscopic signs of OA c: Defined according to unsupervised hierarchical analysis d: Damaged or undamaged cartilage was assessed macroscopically e: Differentially hydroxyMethylated Regions (DhMR) f: Hyper-5-hydroxymethyated g: Hypo-5-hydroxymethyated.