Protease biochemistry

A characteristic feature of OA is the loss of cartilage in affected joints, which causes pain and impairs mobility. This cartilage loss is now understood to be caused by an increase in the activity of destructive ‘enzymes’ that destroy the cartilage structure.

At the Centre, we are trying to understand the molecular signals that cause the activity of these enzymes to increase, so that we can develop strategies to block their activity and protect cartilage. 

SPECIFIC RESEARCH PROJECTS

• The destructive enzymes can be divided into 2 groups - the collagenases and the aggrecanases – with each degrading different parts of the cartilage structure. Studying the detail of how these enzymes attack cartilage will enable us to develop methods to inhibit them in a targeted way.
• OA cartilage has a reduced capacity to clear away these enzymes, and so they are active for longer in OA cartilage than in normal cartilage. Understanding why this clearance pathway is altered in OA is key to restoring cartilage health. 
• OA cartilage has lower levels of a protective inhibitor called TIMP-3 that normally controls the enzymes' destructive activity. In the Centre, we are looking at why this occurs, and at developing therapies to restore healthy levels of the inhibitor.