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MMP-12 and MMP-13 imaging probes describe different waves of protease activities in inflammatory arthritis
MMP-12 and MMP-13 imaging probes describe different waves of protease activities in inflammatory arthritis

Our group is interested in developing molecular imaging probes to study biological processes in vivo and how these processes are affected by osteoarthritis. Currently there are no tools for early diagnosis, prognosis or long term assessment of treatment efficacy for osteoarthritis and we aim to develop probes to fulfil this clinical need.  

In collaboration with Prof. Morten Meldal (University of Copenhagen), we have developed peptide substrate probes which fluoresce upon cleavage by selective members of the matrix-metalloproteinase (MMP) family of enzymes. We have used these probes to describe the early wave of MMP-12 activity and later rise in MMP-13 activity in inflammatory arthritis. This fits in with the understood roles of these enzymes; MMP-12 (macrophage elastase) is necessary for the earlier macrophage migration into the affected tissue, whereas MMP-13 (collagenase-3) is essential for the later destruction of cartilage in this model.  These probes have also been tested in a surgical model of osteoarthritis with some success and we are working to improve this. We are also working on obtaining further selective probes to other metalloproteinases involved in the pathogenesis of osteoarthritis.

These MMP activity probes were imaged using in vivo optical imaging, which has the advantages of being a fast, sensitive and quantitative imaging modality, but limited by low tissue penetration and spatial resolution. To achieve high spatial resolution and deep tissue penetration, we are working on developing a contrast agent for imaging cartilage with micro-computed tomography (microCT). This has the potential to give high resolution images on the status of cartilage without the need for histology post-mortem, which is the current standard method of determining the extent of damage in disease models.  

With an IVIS Spectrum in vivo optical imager and a Quantum FX microCT, The Kennedy Institute of Rheumatology is the ideal place to carry out this research.

Our work is supported through the OA Centre of Excellence, the NC3R and the KTRR. 

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