Matrix Metalloprotease Activity Is an Essential Link Between Mechanical Stimulus and Mesenchymal Stem Cell Behavior
| Autor: | Grit Kasper, Andrea Ode, Georg Matziolis, Juliane D. Glaeser, Jens Tuischer, Sven Geissler, Carsten Perka, Georg N. Duda |
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| Rok vydání: | 2007 |
| Předmět: |
Musculoskeletal Physiological Phenomena
Stimulation Matrix Metalloproteinase Inhibitors Biology Matrix metalloproteinase Mechanotransduction Cellular Models Biological Downregulation and upregulation Matrix Metalloproteinase 13 Humans Regeneration Protease Inhibitors Mechanotransduction Progenitor cell Furin Cells Cultured Aged Aged 80 and over Tissue Inhibitor of Metalloproteinase-2 Mesenchymal stem cell Mesenchymal Stem Cells Tissue Inhibitor of Metalloproteinases Dipeptides Cell Biology Anatomy Middle Aged Matrix Metalloproteinases Cell biology Gene Expression Regulation biology.protein Matrix Metalloproteinase 2 Molecular Medicine Developmental Biology Adult stem cell |
| Zdroj: | Stem Cells. 25:1985-1994 |
| ISSN: | 1549-4918 1066-5099 |
| Popis: | Progenitor cells are involved in the regeneration of the musculoskeletal system, which is known to be influenced by mechanical boundary conditions. Furthermore, matrix metalloproteases (MMPs) and tissue-specific inhibitors of metalloproteases (TIMPs) are crucial for matrix remodelling processes that occur during regeneration of bone and other tissues. This study has therefore investigated whether MMP activity affects mesenchymal stem cell (MSC) behavior and how MMP activity is influenced by the mechanical stimulation of these cells. Broad spectrum inhibition of MMPs altered the migration, proliferation, and osteogenic differentiation of MSCs. Expression analysis detected MMP-2, -3, -10, -11, -13, and -14, as well as TIMP-2, in MSCs at the mRNA and protein levels. Mechanical stimulation of MSCs led to an upregulation of their extracellular gelatinolytic activity, which was consistent with the increased protein levels seen for MMP-2, -3, -13, and TIMP-2. However, mRNA expression levels of MMPs/TIMPs showed no changes in response to mechanical stimulation, indicating an involvement of post-transcriptional regulatory processes such as alterations in MMP secretion or activation. One potential regulatory molecule might be the furin protease. Specific inhibition of MMP-2, -3, and -13 showed MMP-13 to be involved in osteogenic differentiation. The results of this study suggest that MSC function is controlled by MMP activity, which in turn is regulated by mechanical stimulation of cells. Thus, MMP/TIMP balance seems to play an essential role in transferring mechanical signals into MSC function. Disclosure of potential conflicts of interest is found at the end of this article. |
| Databáze: | OpenAIRE |
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