Osteoarthritis Risk Intensifies With Epigenetics

The risk for osteoarthritis has been linked to a number of genes that are susceptible to epigenetic mediators, shows a new review published in Nature Reviews Rheumatology. The influence of epigenetics on osteoarthritis offers new insights on disease risk.

Epigenetics is the mechanism by which the genome alters gene expression without changing the underlying DNA sequence, which in turn affects how cells read the genes. Epigenetic change is a natural occurrence, but can have damaging effects that can result in disease. According to Alegría-Torres et al., “Several lifestyle factors have been identified that might modify epigenetic patterns, such as diet, obesity, physical activity, tobacco smoking, alcohol consumption, environmental pollutants, psychological stress, and working on night shifts." 

The latest review, published in Nature Reviews Rheumatology, is led by John Loughlin, Ph.D., of Newcastle University in the United Kingdom.

Epigenetics plays an important role in regulating the formation and maintenance of joints. Osteoarthritis has a major genetic component, but is also associated with alterations in many epigenetic markers in affected tissues.

In the past few years, genome-wide scans have revealed a large number of osteoarthritis genetic risk loci. Most notably over 90 osteoarthritis susceptibility  loci have been reported for Europeans, the ethnic group that has been most extensively studied. Concurrently, studies of animal and human joint tissues, examining the three major mechanisms of epigenetic regulation, DNA methylation, histone modifications and regulatory RNAs, have investigated joint development, homeostasis and disease.

Data suggest that a large proportion of osteoarthritis genetic risk loci have an effect on epigenetic factors, with consequential changes in gene expression altering the occurrence and progression of osteoarthritis.

Prenatal and early postnatal development of articulating joints is regulated through a number of epigenetic mechanisms. Alterations in these processes can affect the risk of osteoarthritis later in life, such as by changing the joint shape or the cartilage extracellular matrix composition. Studies suggest that epigenetics may help inhibit the disease-causing transition of chondrocytes from an articular to a hypertrophic phenotype as seen in osteoarthritis. In adulthood, epigenetic processes can also be triggered by specific events, such as joint injuries or deregulated metabolism, resulting in osteoarthritis initiation or progression.

“Osteoarthritis might be an age-related disease, but the genetic and epigenetic risk could be functionally active from the beginning of life. If so, such a scenario could provide considerably more time for therapeutic intervention,” the authors wrote. “Epigenetic features are amenable to modulation and, as such, are potential therapeutic targets.”

The authors recommend further study, but suggest that emerging genomic technologies are starting to facilitate the interpretation of the epigenetic effects in osteoarthritis.

REFERENCE

Sarah J. Rice, Frank Beier, David A. Young, et al. “Interplay between genetics and epigenetics in osteoarthritis.”Nature Reviews Rheumatology. April 9, 2020. https://doi.org/10.1038/s41584-020-0407-3