PMID- 19190855 OWN - NLM STAT- MEDLINE DCOM- 20090414 LR - 20090225 IS - 1420-908X (Electronic) IS - 1023-3830 (Linking) VI - 58 IP - 3 DP - 2009 Mar TI - Telopeptides of type II collagen upregulate proteinases and damage cartilage but are less effective than highly active fibronectin fragments. PG - 161-9 LID - 10.1007/s00011-009-8090-5 [doi] AB - 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 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. FAU - Guo, D AU - Guo D AD - Department of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, 58202, USA. FAU - Ding, L AU - Ding L FAU - Homandberg, G A AU - Homandberg GA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - Switzerland TA - Inflamm Res JT - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JID - 9508160 RN - 0 (Collagen Type II) RN - 0 (Fibronectins) RN - 0 (Interleukin-1beta) RN - 0 (Peptide Fragments) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.4.24.- (ADAM Proteins) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - ADAM Proteins/metabolism MH - Amino Acid Sequence MH - Animals MH - Cartilage, Articular/metabolism/*pathology MH - Cattle MH - Cells, Cultured MH - Chondrocytes/cytology/metabolism MH - Collagen Type II/genetics/*metabolism MH - Fibronectins/genetics/*metabolism MH - Humans MH - Interleukin-1beta/immunology MH - Matrix Metalloproteinases/metabolism MH - Molecular Sequence Data MH - Osteoarthritis/metabolism/pathology MH - Peptide Fragments/genetics/*metabolism MH - Tumor Necrosis Factor-alpha/immunology EDAT- 2009/02/05 09:00 MHDA- 2009/04/15 09:00 CRDT- 2009/02/05 09:00 PHST- 2009/02/05 09:00 [entrez] PHST- 2009/02/05 09:00 [pubmed] PHST- 2009/04/15 09:00 [medline] AID - 10.1007/s00011-009-8090-5 [doi] PST - ppublish SO - Inflamm Res. 2009 Mar;58(3):161-9. doi: 10.1007/s00011-009-8090-5.