Cleavage of Cartilage Oligomeric Matrix Protein (COMP) by ADAMTS4 generates a neoepitope associated with osteoarthritis severity and progression

The major proteoglycan in cartilage is COMP. This protein undergoes extensive proteolytic turnover that is believed to be dysregulated during osteoarthritis. Here we identify and describe two secreted proteases that are responsible for this turnover and identify the specific sites of proteolysis by each protease. This data was used to generate a neo-epitope antibody for validating these cleavage sites in human tissues.