Cleavage of Cartilage Oligomeric Matrix Protein (COMP) by ADAMTS4 generates a neoepitope associated with osteoarthritis and other forms of degenerative joint disease.

Osteoarthritis (OA) is a highly prevalent joint disease, affecting millions of people worldwide and characterized by degradation of articular cartilage, subchondral bone remodeling and low-grade inflammation, leading to pain, stiffness and disability. Cartilage Oligomeric Matrix Protein (COMP) is a major structural component of cartilage and its degradation has been proposed as a marker of OA severity/progression. Several proteases cleave COMP in vitro, however, it is unclear which of these COMPase activities is prevalent in an osteoarthritic joint.

Concizumab prophylaxis in people with haemophilia A or haemophilia B without inhibitors (explorer8): a prospective, multicentre, open-label, randomised, phase 3a trial.

Background: Concizumab is an anti-tissue factor pathway inhibitor monoclonal antibody in development as a once-daily, subcutaneous prophylaxis for patients with haemophilia A or haemophilia B with or without inhibitors. We aimed to assess the efficacy and safety of concizumab in patients with haemophilia A or B without inhibitors. Here we report the results from the confirmatory analysis cutoff.

Degradomics defines proteolysis information flow from human knee osteoarthritis cartilage to matched synovial fluid and the contributions of secreted proteases ADAMTS5, MMP13 and CMA1 to articular cartilage breakdown.

Objectives: Proteolytic cartilage extracellular matrix breakdown is a major mechanism of articular cartilage loss in osteoarthritis (OA) pathogenesis. We sought to determine the overlap of proteolytic peptides in matched knee OA cartilage and synovial fluid on a proteome-wide scale to increase the prospective biomarker repertoire and to attribute proteolytic cleavages to specific secreted proteases.

Design: Matched human knee OA cartilage and synovial fluid (n = 5) were analyzed by N-terminomics using Terminal Amine Isotopic Labeling of Substrates (TAILS), comprising labeling and enrichment of protein N-termini, high-resolution mass spectrometry and positional peptide mapping.