Matrix metalloproteinase-13 influences ERK signalling in articular rabbit chondrocytes

Raggatt, L. J., Jefcoat, S. C., Choudhury, I., Williams, S., Tiku, M. and Partridge, N. C. (2006) Matrix metalloproteinase-13 influences ERK signalling in articular rabbit chondrocytes. Osteoarthritis and cartilage, 14 7: 680-689. doi:10.1016/j.joca.2006.01.006

Author Raggatt, L. J.
Jefcoat, S. C.
Choudhury, I.
Williams, S.
Tiku, M.
Partridge, N. C.
Title Matrix metalloproteinase-13 influences ERK signalling in articular rabbit chondrocytes
Journal name Osteoarthritis and cartilage   Check publisher's open access policy
ISSN 1063-4584
Publication date 2006-07-01
Year available 2006
Sub-type Article (original research)
DOI 10.1016/j.joca.2006.01.006
Open Access Status
Volume 14
Issue 7
Start page 680
End page 689
Total pages 10
Place of publication London
Publisher Published for the Society by Baillière Tindall
Language eng
Subject 110314 Orthopaedics
110322 Rheumatology and Arthritis
Abstract Summary Objective Matrix metalloproteinase-13 (MMP-13) is an extracellular MMP that cleaves type II collagen, the major protein component of cartilage, with high specificity and has been implicated in the pathology of osteoarthritis. The present study aimed to characterize the binding and internalization kinetics of MMP-13 in normal rabbit chondrocytes and whether MMP-13 affected cell signalling. Methods Rabbit chondrocytes were used in [125I]-MMP-13 binding assays to investigate the MMP-13 binding kinetics and Western analysis allowed for the assessment of intracellular signalling cascades. Results Rabbit chondrocytes were found to express the cartilage-specific genes aggrecan and type II collagen throughout their in vitro culture period. Appreciable specific cell-association of [125I]-MMP-13 was detected after 10 min of exposure to the ligand and equilibrium was obtained after 2 h. Binding of [125I]-MMP-13 to chondrocytes was specific and approached saturation at 75 nM. Internalization of MMP-13 was evident after 20 min, reached a maximum at 30 min and had returned to baseline by 90 min. Addition of receptor-associated protein (RAP) inhibited the internalization of MMP-13 indicating a likely role for low-density lipoprotein receptor-related protein-1 (LRP1) in this process. Interestingly the presence of MMP-13 induced phosphorylation of the extracellular signal-regulated kinase 1/2 (ERK1/2) protein showing that there is initiation of a signalling process in response to MMP-13 being bound and internalized by rabbit chondrocytes. However, this activation does not involve the MMP-13 internalization receptor LRP1. Conclusion These studies demonstrate and characterize the MMP-13 binding and internalization system in rabbit chondrocytes and indicate that MMP-13 may regulate the phenotype of the chondrocytes through this receptor system
Keyword MMP-13
Matrix metalloproteinases
Q-Index Code C1
Grant ID AR40661
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
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