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Does our body clock hold the key to developing new treatments for arthritis?

Arthritis Today Spring 2018 Issue 175An alarm clock in front of a sleeping womanMost of us will have felt the temporary effects of a disrupted body clock, whether it’s caused by a long flight, a changing shift pattern or even just a few late nights. But scientists all over the world now recognise the importance of our biological clocks to lifelong health and well-being.

In 2014 Arthritis Research UK invested more than a million pounds into two five-year studies at the University of Manchester investigating how disruption to our daily circadian rhythms is linked to osteoarthritis and inflammatory arthritis. In this edition we’re reporting on how this exciting new research is building our understanding of the role the body clock plays in arthritis and how this knowledge is being used to develop new and more effective treatments.

What's the body clock and what are circadian rhythms? 

The body clock is an innate daily timing device, found in most living things. A biological clock ticks in almost every cell in the human body, driving circadian rhythms.

Circadian rhythms are physical, mental and behavioural changes that follow a 24-hour cycle. They're controlled primarily by light and darkness in the environment.

Circadian rhythms influence how our bodies work, from when we go to sleep and wake up to when hormones are released, from our eating habits and digestion to our body temperature. A fast- or slow-running body clock can disrupt circadian rhythms, having a negative impact on our health and well-being.

The body clock, ageing and osteoarthritis

Research led by Qing-Jun Meng, Professor of Chronobiology at The University of Manchester, is exploring how the ageing process affects our body clocks and how this relates to osteoarthritis. Professor Meng explains:

"The body clock is a result of evolution, helping organisms to anticipate and adapt to the time of day so they can survive in a changing environment. We need this daily control to optimise the everyday workings of the human body, so a disrupted body clock can stop the body from working as it should."

Research shows as we age our body clocks can move out of sync and our circadian rhythms are dampened down. Professor Meng’s study began looking at what impact this body clock disruption has on the articular cartilage, the smooth tissue covering the ends of our bones where they come together to form joints. Healthy cartilage in our joints allows the bones to glide over each other but when a person has osteoarthritis this cartilage degenerates, leading to joint pain and stiffness. He says:

"Through our research we’ve discovered the circadian rhythms in this cartilage control the repair and degeneration of tissue. We’ve identified that there are certain points during the 24-hour cycle when cartilage tissue breaks down, for example while the joints are moving, and other times when it is repaired.

"Tissue repair can’t happen at the same time as the damage is being done; it'd be like trying to build a wall while someone else is knocking it down. So, our bodies have found a way to separate these tasks and allow specific times each day for tissue repair."

The researchers’ next step was to test just how important the circadian rhythms were to the tissue’s ability to repair itself. Professor Meng continues: "We can remove a specific gene from a cell to eliminate that cell’s body clock and cause its circadian rhythms to flatline. When we deleted this gene in cartilage tissue in mice we saw clear signs of accelerated ageing and cartilage damage."Removing the biological clocks from these cells led to tissue degeneration, suggesting the body clock plays a crucial role in keeping tissue healthy."Professor Qing-Jun Meng 

"Removing the biological clocks from these cells led to tissue degeneration, suggesting the body clock plays a crucial role in keeping tissue healthy and helping the tissue to repair itself if it does get damaged."

This was a breakthrough in both body clock research and our understanding of osteoarthritis. The research team is currently exploring if it's possible to devise new treatments to boost these dampened circadian rhythms in cartilage tissue to prevent damage and keep cartilage healthy.

Professor Meng says: "Studies like ours are giving a fresh perspective on osteoarthritis. We’re working on innovative solutions, using both medical devices and drugs, that could help us to keep the body clocks in cartilage tissue working as they should even as people age.

"We hope our findings will mean in future we can improve quality of life for people with osteoarthritis, delaying damage in the joints and reducing pain and the need for joint replacement surgery."

The body clock, our immune system and rheumatoid arthritis

Developing a better understanding of the relationship between the body clock and the immune system, and how together they affect inflammation in the body, is the focus of Dr Julie Gibbs’ research. She explains: "The body clock controls how our immune system works every day to protect us; it helps to maintain its balance. Research in both animals and humans shows if the body clock is disrupted over a period of days this has a negative impact on the immune system.

"Irregular circadian rhythms can prevent our bodies from being able to deal with daily challenges and bigger threats like infection or the inflammation seen in rheumatoid arthritis."Greater understanding of the 24-hour cycle could help to identify times when drug treatments might be more effective or have fewer side-effects.

The study set out to map and explore daily patterns in inflammation. Greater understanding of the 24-hour cycle could help to identify key times when new and existing drug treatments for rheumatoid arthritis might be more effective or have fewer side-effects. Dr Gibbs says: "People with inflammatory arthritis often report having their worst symptoms early in the morning. Our study set out to look at why that is and to find out if increased inflammation at certain times of day was because of the immune system responding to circadian rhythms.

"When we looked at cells in the joints of mice over a 24-hour period we found there was far less inflammation during the night. We discovered this reduced inflammation was associated with the higher levels of cryptochrome present in the cells at night. Cryptochrome is a protein that’s involved in the body clock’s machinery. When we translated these findings to testing with human cells they showed the same pattern.

"We're now looking at the possibility of changing the time of day when anti-inflammatory drugs already on the market are taken to improve their effectiveness. We’re also investigating the potential of new drug treatments which could improve how the body clock works. We hope that in the future research in this area could lead to new treatment options which will impact positively on the lives of people with rheumatoid arthritis."

Tips to maintain a health body clock

A regular daily schedule helps to enhance circadian rhythms and keep our body clock synchronised with our environment, which is good for our health and well-being. Here are some tips on how to maintain a healthy body clock:

  • Establish a routine of going to bed and waking up at a similar time each day, including weekends.
  • Keep the bedroom dark and don’t look at screens before bed. Exposure to light inhibits the production of melatonin, which is what makes us drowsy and ready to sleep.
  • Stick to regular mealtimes and eat a healthy diet as food also affects the body clock.

Read next: Can community walking programmes help people with arthritis to Walk with Ease?

A group of people taking part in the Walking with Ease study

When you're dealing with pain and fatigue, keeping active can feel like a real challenge. That’s why researchers are exploring the benefits of a community walking programme designed for people with arthritis.

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