The treatment of cartilage with mediators initiates the breakdown of proteoglycan followed by collagen. This is accompanied by the modulation of different proteinases and inhibitors that include members of the MMP family and TIMPs. We have evidence that a chondrocyte membrane-associated metalloproteinase cleaves aggrecan. This activity is rapidly induced after stimulation with IL-1 and OSM and is not inhibited by TIMPs-1 and -2 but is inhibited by synthetic MMP inhibitors. This same combination of cytokines also upregulates the collagenases with the subsequent release of collagen fragments, and there is a close correlation between the amount of collagen released and collagenase activity produced. Collagen release can be prevented after treatment with specific inhibitors of MAP kinases, inhibitors of MMP transcription, synthetic metalloproteinase inhibitors, TIMPs and treatment of cartilage with agents that upregulate TIMPs. The results from bovine cartilage culture models show that collagen release occurs when TIMP levels are low, collagenases are upregulated and then subsequently activated.

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The breakdown of aggrecan in cartilage is, in part, mediated by an enzyme named aggrecanase that cleaves within the interglobular domain of the molecule between a glutamic residue and an alanine residue. Although the enzyme cleavage site has been identified, the identity, characteristics and localization of this enzyme remain unclear. We have demonstrated that membranes isolated from stimulated chondrocytes are able to generate aggrecan fragments that are labelled by an antibody that recognizes the new N-terminus formed by aggrecanase activity. It was further shown that the membrane activity was a metalloproteinase but was not inhibited by the naturally occurring matrix metalloproteinase (MMP) inhibitors, TIMPs 1 and 2. These results show that an aggrecanase activity is associated with the membranes of the chondrocytes and is a metalloproteinase, but might not be a member of the MMP family.

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In 2011, the Leicestershire Clinical Genetics Department in collaboration with Macmillan Cancer Support initiated a project called Supporting Families with Cancer (SFWC). The project aimed to raise awareness of inherited cancers amongst both healthcare professionals and the general public and develop a patient-centred collaborative approach to cancer treatment and support services. This paper describes the project's development of a range of community outreach events and a training scheme for primary healthcare professionals designed to improve familial cancer referral rates in Leicester. Following consultation with patients and support groups, a series of interactive 'medical supermarket' events were held in Leicester. These events focused on providing patients with a forum for sharing research data, information about diagnosis and treatments and access to support groups and other allied healthcare services with additional information being made available digitally via SFWC webpages and a series of short videos available on a YouTube channel. Qualitative and quantitative data presented here indicate that the SFWC medical supermarket model has been well received by patients and offers a patient-centred, holistic approach to cancer treatment.