Forward and reverse degradomics defines the proteolytic landscape of human knee osteoarthritic cartilage and the role of the serine protease HtrA1

Proteolytic destruction of articular cartilage is a major pathogenic mechanism in osteoarthritis (OA), but was not previously investigated on a proteome-wide scale. We sought to define the human knee OA cartilage degradome and the contribution therein of the serine protease HtrA1, using an N-terminomics strategy, terminal amine isotopic labeling of substrates (TAILS).