Dec, 2016
MMP-13 is constitutively produced in human chondrocytes and co-endocytosed with ADAMTS-5 and TIMP-3 by the endocytic receptor LRP1
MATRIX BIOLOGY
- Volume
- 56
- Number
- First page
- 57
- Last page
- 73
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1016/j.matbio.2016.03.007
- Publisher
- ELSEVIER SCIENCE BV
Matrix metalloproteinase 13 (MMP-13) degrades collagenous extracellular matrix and its aberrant activity associates with diseases such as arthritis, cancer, atherosclerosis and fibrosis. The wide range of MMP-13 proteolytic capacity suggests that it is a powerful, potentially destructive proteinase and thus it has been believed that MMP-13 is not produced in most adult human tissues in the steady state. Present study has revealed that human chondrocytes isolated from healthy adults constitutively express and secrete MMP-13, but that it is rapidly endocytosed and degraded by chondrocytes. Both pro- and activated MMP-13 bind to clusters II and III of low-density lipoprotein (LDL) receptor-related protein 1 (LRP1). Domain deletion studies indicated that the hemopexin domain is responsible for this interaction. Binding competition between MMP-13 and ADAMTS-4,-5 or TIMP-3, which also bind to cluster II, further shown that the MMP-13 binding site within cluster II is different from those of ADAMTS-4,-5 or TIMP-3. MMP-13 is therefore co-endocytosed with ADAMTS-5 and TIMP-3 by human chondrocytes. These findings indicate that MMP-13 may play a role on physiological turnover of cartilage extracellular matrix and that LRP1 is a key modulator of extracellular levels of MMP-13 and its internalization is independent of the levels of ADAMTS-4,-5 and TIMP-3. (C) 2016 The Authors. Published by Elsevier B.V.
- Link information
-
- DOI
- https://doi.org/10.1016/j.matbio.2016.03.007
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/27084377
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5146981
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000389784800004&DestApp=WOS_CPL
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84963983808&origin=inward Open access
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84963983808&origin=inward
- ID information
-
- DOI : 10.1016/j.matbio.2016.03.007
- ISSN : 0945-053X
- eISSN : 1569-1802
- Pubmed ID : 27084377
- Pubmed Central ID : PMC5146981
- SCOPUS ID : 84963983808
- Web of Science ID : WOS:000389784800004