Abstract.
Objective and Design:
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).
Materials:
NT and CT peptides were synthesized.
Methods:
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.
Results:
NT and CT peptides penetrated cartilage, bound to chondrocytes and enhanced proteinase release and cartilage PG depletion. Peptides had detectable activity at 0.3 μM (1 μg/ml) and were comparable at 30 μM (100 μg/ml) to 1 μM Fn-f (29 μg/ml). However, while the Fn-f enhanced IL-1β and TNF-α, the NT and CT peptides did not.
Conclusions:
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 μg/ml, they have the potential to play a role in physiologic cartilage damage.
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Received 7 May 2008; returned for revision 9 June 2008; received from final revision 8 July 2008; accepted by J. A. Battista 31 July 2008
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Guo, D., Ding, L. & Homandberg, G.A. Telopeptides of type II collagen upregulate proteinases and damage cartilage but are less effective than highly active fibronectin fragments. Inflamm. Res. 58, 161–169 (2009). https://doi.org/10.1007/s00011-009-8090-5
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DOI: https://doi.org/10.1007/s00011-009-8090-5