The activity “blind spot”: Why understanding which proteinases are active, not merely present, is essential for rigorous osteoarthritis research

Joint destruction in OA is governed not by proteinase expression alone, but by tightly regulated spatial and temporal activation. Hence, abundance-based measurements can substantially overestimate functional proteolysis. Greater emphasis on direct or proxy measures of activity - conceptualized as the proteinase "activome" - will strengthen experimental interpretation, improve disease stratification, and support discovery of activity-based biomarkers and therapeutic strategies.