Epigenetic Regulation in Knee Osteoarthritis

Abstract

Osteoarthritis (OA) is a complicated disease with both hereditary and environmental causes. Despite an increase in reports of possible OA risk loci, it has become clear that genetics is not the sole cause of osteoarthritis. Epigenetics, which can be triggered by environmental influences and result in transcriptional alterations, may have a role in OA pathogenesis. The majority of recent research on the epigenetics of OA has been focused on DNA methylation, histone modification, and non-coding RNAs. However, this study will explore epigenetic regulation in OA at the present stage. How genetics, environmental variables, and epigenetics interact will be researched, shedding light for future studies. Their possible interaction and control processes open up new avenues for the development of innovative osteoarthritis treatment and diagnostic techniques.

Keywords: DNA methylation; epignetics; histone modification; knee osteoarthritis; noncoding RNA.

FIGURE 1

Risk factors of knee OA. Risk factors for knee osteoarthritis includes ageing, gender, injury, and joint overloading, etc. Epigenetics may play a considerable role in how these environmental factors lead to altered gene expression and ultimately pathophysiologic manifestations such as cartilage damage and subchondral osteosclerosis.

FIGURE 2

Methylation and demethylation of DNA. In methylation process, the 5′carbon of cytosine was methylated to 5-MC with S-adenosine methionine (SAM) as the methyl donor. During active demethylation, the methyl group of 5 mC can be modified by the TETs-mediated addition of hydroxyl groups to generate 5-hydroxymethylcytosine (5hmC), which can be subsequently processed in demethylation process.

FIGURE 3

A model for the presence of altered levels of DMR methylation due to specific risk alleles is shown here. Certain OA-associated SNP mutations may lead to alterations in the degree of DMR methylation at a distance from the associated causative gene, which affects the expression of the associated gene. This unique mode of action is better studied and defined in the locus of chromosome 6p21.1 labelled rs10948172, with the associated gene RUNX2 (Zhang G. et al., 2020).

FIGURE 4

histone modification. Histone acetylase (HAT) and Histone deacetylase (HDAC) are two classes of enzymes responsible for the structural modification of chromosomes and regulation of gene expression. In general, acetylation of histones facilitates the dissociation of DNA from histone octamers and the relaxation of nucleosome structure, thus allowing various transcription factors and co-transcription factors to bind specifically to DNA binding sites and activate gene transcription. In contrast, deacetylation of histones exerts the opposite effect with Histone acetylase.