DNA METHYLATION PROFILING IN KNEE TISSUES: A PILOT EPIGENETIC INVESTIGATION INTO OBESITY ASSOCIATED OSTEOARTHRITIS

Helen McCarthy, Karina Wright, Martyn Snow, Jan-Herman Kuiper, Charlotte Hulme

Osteoarthritis (OA) is a common joint condition that causes pain and reduced mobility, affecting nearly 8% of people worldwide. Obesity is a major risk factor for OA and is present in around 1 in 5 people with the disease. Obese individuals have twice the lifetime risk of developing painful OA compared to those of a healthy weight. This increased risk is partly due to extra weight pressure on the joints, but also because obesity triggers chronic low-level inflammation that affects joint health.

One key area of joint inflammation is the joint lining, called the synovium. Inflammation here, known as synovitis, contributes to joint pain and disease progression. Although weight loss is often recommended, it does not always slow OA progression. This raises the question of whether obesity causes lasting biological changes that continue even after weight loss.

Recent research suggests that obesity may leave behind a type of “molecular memory” through a process called epigenetics, where the activity of genes can be changed without altering the DNA itself (see picture insert). One such mechanism is DNA methylation, which can switch genes on or off. We know obesity can change DNA methylation in fat tissue, but it is unclear if similar changes occur in joint tissues.

This study explores whether obesity alters DNA methylation patterns in cartilage and synovial tissue from people with OA. By comparing tissues from obese and non-obese patients undergoing knee replacement surgery, we aim to identify specific epigenetic changes linked to inflammation and OA severity. This will help us understand how obesity contributes to joint damage and could support the development of more personalised treatments for people living with both obesity and OA.