期刊
MATRIX BIOLOGY
卷 56, 期 -, 页码 57-73出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.matbio.2016.03.007
关键词
Cartilage; Endocytosis; Extracellular trafficking; Matrix metalloproteinases; Collagenase; Osteoarthritis
资金
- Arthritis Research UK [20563, 19466]
- Arthritis Research UK Centre for Osteoarthritis Pathogenesis [20205]
- Kennedy Trust for Rheumatology Research
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [AR40994]
- National Heart, Lung and Blood Institute [HL072929, HL114379]
- Grants-in-Aid for Scientific Research [26670665, 25461110, 26293338] Funding Source: KAKEN
- Versus Arthritis [20563, 19466] Funding Source: researchfish
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.
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