Understanding the role of tissue degrading enzymes and their inhibitors in development and disease.
Cartilage and the underlying bone are destroyed in severe cases of arthritis preventing joints from functioning normally. Cartilage and bone collagen can be specifically cleaved by the collagenases, members of the matrix metalloproteinase family (MMPs), whilst cartilage aggrecan is degraded by members of the ADAMTS (A Disintegrin And Metalloproteinase with ThromboSpondin repeats) family of proteinases. Intracellular cysteine proteinases are involved in bone resorption by osteoclasts and the serine proteinases are involved in activating MMPs. Together, these enzymes act in concert during normal growth and development, especially within the growth plate; however they are also involved in tissue destruction during disease. Synthetic MMP inhibitors have been investigated as a means to block tissue destruction in arthritis but have been unsuccessful, although recent trials with doxycycline suggest this may block joint destruction in osteoarthritis. It is likely that combinations of therapy will be required to ensure that joint destruction is prevented in arthritis patients.
Cawston
Tim E
TE
Musculoskeletal Research Group, 4th Floor Cookson Building, The Medical School, University of Newcastle upon Tyne, NE2 4HH, UK. T.E.Cawston@ncl.ac.uk
Wilson
Amy J
AJ
D051722:ADAM Proteins / Q000502:physiology*; D001168:Arthritis / Q000201:enzymology* / Q000503:physiopathology*; D002358:Cartilage, Articular / Q000201:enzymology / Q000473:pathology; D003546:Cysteine Endopeptidases / Q000502:physiology; D015870:Gene Expression; D006132:Growth Plate / Q000201:enzymology; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism / Q000502:physiology*; D010447:Peptide Hydrolases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship
D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases