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


METHODS
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 microM (1 microg/ml) and were comparable at 30 microM (100 microg/ml) to 1 microM Fn-f (29 microg/ml). However, while the Fn-f enhanced IL-1beta and TNF-alpha, 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 microg/ml, they have the potential to play a role in physiologic cartilage damage.
Guo
D
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Department of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, 58202, USA.
Ding
L
L
Homandberg
G A
GA
D051722:ADAM Proteins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D024043:Collagen Type II; D005353:Fibronectins; D053583:Interleukin-1beta; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases