| Title |
MMP-13 is constitutively produced in human chondrocytes and co-endocytosed with ADAMTS-5 and TIMP-3 by the endocytic receptor LRP1
|
|---|---|
| Published in |
Matrix Biology, April 2016
|
| DOI | 10.1016/j.matbio.2016.03.007 |
| Pubmed ID | |
| Authors |
Kazuhiro Yamamoto, Hiroshi Okano, Wakako Miyagawa, Robert Visse, Yasuyuki Shitomi, Salvatore Santamaria, Jayesh Dudhia, Linda Troeberg, Dudley K. Strickland, Satoshi Hirohata, Hideaki Nagase |
| Abstract |
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. |
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Mendeley demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Canada | 1 | <1% |
| Unknown | 175 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 29 | 16% |
| Student > Bachelor | 19 | 11% |
| Student > Master | 16 | 9% |
| Student > Doctoral Student | 9 | 5% |
| Researcher | 9 | 5% |
| Other | 27 | 15% |
| Unknown | 67 | 38% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 41 | 23% |
| Medicine and Dentistry | 20 | 11% |
| Agricultural and Biological Sciences | 13 | 7% |
| Engineering | 10 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 6 | 3% |
| Other | 16 | 9% |
| Unknown | 70 | 40% |