Project 451443

Osteoarthritis is a chronic disease of the joints with no available disease modifying treatments. The changes that happen when a knee joint goes from being healthy to arthritic are not completely understood but an increase in a group of proteins called 'enzymes', that can cut other proteins is noted. In addition to destroying the tissue in the knee, these enzymes can also cause inflammation and pain by turning on a family of proteins called PARs. In this proposal we wish to specifically characterize the enzymes that are present in the knee joints of human osteoarthritis patients that can turn on the PARs. This will allow us to develop strategies for preventing the PARs from turning on and this in turn will suppress the inflammation and pain that make osteoarthritis a chronic and debilitating disease. We have assembled a team of physicians, surgeons and scientists to tackle this exciting project. We have also developed unique biosensors and transgenic mice that will allow us to successfully complete this work. Our studies are guided by preliminary findings in human patients, with studies at the cell and molecular level and in pre-clinical animal models helping us to identify the best strategies for treatment that can then be tested further in the clinic.