Non-animal models for investigating osteoarthritis

We have developed a novel non-animal model to study osteoarthritis. The ex-vivo system applies mechanical loading to cartilage cells taken from the joints of animals that normally would be abbatoir waste material and examines the effect of loading at reduced oxygen levels. This ex-vivo environment is similar to a knee joint experienced when a person is walking or does moderate exercise.

Our previous research showed that mechanical loading of cartilage cells helps to control the levels of molecules which speed up the breakdown of cartilage. We knew that fragments of certain molecules in cartilage are harmful and their presence increases cartilage loss and progresses the disease. What we did not know is whether reduced oxygen tension which are conditions similar to a diseased environment in combination with mechanical loading, could control the levels of the harmful fragment molecules and prevent cartilage loss, slowing down or even stopping the disease. Our early work showed that loading affects this process and can benefit the cartilage tissue. However, the exact way this happened was not known.

We used a non-animal model to find out more about this process. We grew cartilage cells in a 3D jelly-like environment at low oxygen tension whilst simultaneously applying mechanical loading. We found that the fragment molecules increased the production of the harmful inflammatory molecules and this process was enhanced further at low oxygen tension causing damage to cartilage tissue.  However when mechanical loading was applied to cells in the presence of the harmful fragment molecules, their actions were prevented and the cartilage tissue was able to repair itself despite the low level of oxygen tension.

We are the first to examine the combined effect of both loading and oxygen tension on the action of fragments and show that exercise is beneficial whatever the oxygen tension.

Our encouraging data gives us the confidence to explore more about this process and find out exactly how loading prevents the damaging effects caused by fragments. By investigating the process in non-animal models, be will be able to design new training protocols or therapies that help people with joint damage and support a healthy cartilage phenotype during old age. 

The work was published in https://link.springer.com/article/10.1007%2Fs00011-016-0991-5

The project supported Reshma Tilwani during her PhD awarded in 2017.

https://www.sems.qmul.ac.uk/news/4529/phd-success-for-sems-students-michal-and-reshma

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