Fig. 2.

Formation of stable multivalent cross-links in the ECM. Lysine residues within elastin and collagen are firstly converted into hydroxy-lysine residues by lysyl hydroxylase, then peptidyl lysine and/or hydroxy-lysine residues both serve as the precursors of cross-links and undergo the oxidative deamination catalyzed by the LOX family (LOXs), and unstable aldehydes are generated. The resulting aldehydes then react with neighboring lysine residues or with other peptidyl aldehyde residues spontaneously through Schiff’s base formation or aldol condensation to generate intra- and intermolecular covalent cross-links, leading to the formation of immature dehydroxylysinorleucine (DHLNL) cross-links which are converted into stable pyridinoline (PYR) cross-links, the main type of cross-links in the extracellular matrix (ECM) of cartilage