Telopeptides of type II collagen upregulate proteinases and damage cartilage but are less effective than highly active fibronectin fragments

We hypothesize that N-telopeptide (NT) and C-telopeptides (CT) of type II collagen can enhance proteinases and cause cartilage damage and have compared damaging activities to an extensively characterized potent fibronectin fragment (Fn-f). NT and CT peptides were synthesized. Interaction of labeled peptides with chondrocytes was studied by fluorescence microscopy. Effects on the metalloproteinases (MMPs) MMP-3 and MMP-13 and on ADAMTS-5 were analyzed by western blotting. Cartilage damage was assayed by loss of proteoglycan (PG) from cultured explants. NT and CT peptides penetrated cartilage, bound to chondrocytes and enhanced proteinase release and cartilage PG depletion. Peptides had detectable activity at 0.3 mu M (1 mu g/ml) and were comparable at 30 mu M (100 mu g/ml) to 1 mu M Fn-f (29 mu g/ml). However, while the Fn-f enhanced IL-1 beta and TNF-alpha, the NT and CT peptides did not. Collagen peptides containing NT and CT regions were less active on a molar basis than Fn-fs but were still potent damaging agents. Since collagen fragments are found in OA cartilage at mu g/ml, they have the potential to play a role in physiologic cartilage damage.