Discovery of the enzyme that destroys cartilage in inflammatory arthritis

A Melbourne-led team of scientists has discovered the enzyme that destroys cartilage in inflammatory arthritis, offering new hope to sufferers of this painful condition.

From the University of Melbourne’s Department of Paediatrics and Murdoch Childrens Research Institute, Dr Amanda Fosang says the research is the first to report a single enzyme deficiency that can protect against arthritis.

The findings will be published in Nature on Thursday 31 March.

Dr Fosang says cartilage is found throughout the body, most notably covering bone endings in joints such as the knee and hip. A large molecule called aggrecan gives cartilage its unique capacity to bear load and resist compression and it is this substance that is broken down in arthritis. The result is a weak cartilage and painful joints.

To date, the enzyme responsible for breaking down aggrecan has not been known.

“Our new findings, which examined the activities of a range of enzymes in mice, identified a single enzyme called ADAMTS5 which was the main culprit for aggrecan breakdown,” Dr Fosang says.

“This means that ADAMTS5 may be a suitable target for the development of new drugs designed to inhibit cartilage destruction in arthritis and could have practical implications for both children and adults who suffer from the condition.”

The researchers will now embark on studies to investigate what turns ADAMTS5 on and off and why it is overly active in arthritis.

The research involved collaboration between the University of Melbourne, Murdoch Childrens Research Institute, the Walter and Eliza Hall Institute of Medical Research and Johnson & Johnson.