Cartilage Cells Have Body Clock: Effect on OA?

Researchers from the University of Manchester have determined for the first time that cartilage cells have a body clock that switches on and off genes controlling tissue function. The rhythm of the cartilage clock perhaps goes some way to explain why osteoarthritis (OA) sufferers find the symptoms of the disease worse at certain times of the day. This work was led by Dr. Qing-Jun Meng, MRC (Medical Research Center) Career Development Award Fellow in the
Faculty of Life Sciences
at the University of Manchester in the UK.

When Dr. Qing-Jun Meng and his team studied cartilage tissue in older mice they found that the tissue’s body clock was 40% weaker than in younger mice. This suggested that clock deterioration could contribute to an increased risk of developing OA in later life. The researchers then looked at cartilage cells affected by damage similar to osteoarthritis and found that components of the body clock are altered during the early stages of the disease.

In the June 11, 2013 news release Dr. Meng says: “By imposing a rhythm to boost the internal rhythm in cartilage, our data suggests the aged cartilage clock might be re-tuned. This could be done using systemic approaches such as scheduled exercise, restricted meal times or by targeting the joint itself with scheduled warming and cooling. We believe imposing a rhythm could have a significant impact on the future management of joint diseases and with further study it could relieve sufferers’ symptoms.”

Dr. Meng and his team have now been awarded an MRC grant of half a million pounds to establish the causal relationship between clock disruptions and the onset and severity of osteoarthritis as well as identifying novel therapeutic targets.

Asked what are the most important things for orthopedic surgeons to know about this work, Dr. Meng commented to OTW, “That there is a functional body clock in the joint cartilage which rhythmically controls 4% of genes in this tissue. Also, during aging, the cartilage rhythm deteriorates, which may explain the increased risk to diseases such as osteoarthritis, symptoms of which demonstrate time-of-day effects. The rhythmic nature in gene expression calls for novel therapeutic approaches that take into consideration the timing of interventions, so called ‘chronotherapy’, i.e., timed-delivery of drugs/treatments. Temperature cycles that mimic daily body temperature changes are capable of strengthening the cartilage clocks, which could be developed into a new non-invasive approach to slow down or reverse the progression of joint diseases.”

Looking forward, Dr. Meng told OTW, “Future research will test the potential causal role of cartilage clock disruptions to the development of osteoarthritis, using transgenic animals that have chondrocyte-specific clock gene deletion. Systemic (light/dark cycle or temperature rhythm) or pharmacological approaches that target the cartilage rhythms will also be tested in experimental models of osteoarthritis.”