Complementary Roles of Intracellular and Pericellular Collagen Degradation Pathways In Vivo
Autor: | Niels Behrendt, Julie Gavard, Kenn Holmbeck, Susan S. Yamada, Lars H. Engelholm, J. Silvio Gutkind, Thomas H. Bugge, Rebecca A. Wagenaar-Miller |
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Rok vydání: | 2007 |
Předmět: |
Connective tissue
Mice Inbred Strains Receptors Cell Surface In situ hybridization Biology Receptors Urokinase Plasminogen Activator Mice Mice Congenic Chondrocytes Bone Density Osteogenesis In vivo Matrix Metalloproteinase 14 medicine Animals Hematoxylin Molecular Biology Alleles Cells Cultured In Situ Hybridization Mice Knockout Metalloproteinase Osteoblasts Cartilage Skull Cell migration Articles Cell Biology Immunohistochemistry Cell biology medicine.anatomical_structure Animals Newborn Biochemistry Receptors Mitogen Eosine Yellowish-(YS) Collagen Tomography X-Ray Computed Intracellular |
Zdroj: | Molecular and Cellular Biology. 27:6309-6322 |
ISSN: | 1098-5549 |
Popis: | Collagen degradation is essential for cell migration, proliferation, and differentiation. Two key turnover pathways have been described for collagen: intracellular cathepsin-mediated degradation and pericellular collagenase-mediated degradation. However, the functional relationship between these two pathways is unclear and even controversial. Here we show that intracellular and pericellular collagen turnover pathways have complementary roles in vivo. Individual deficits in intracellular collagen degradation (urokinase plasminogen activator receptor-associated protein/Endo180 ablation) or pericellular collagen degradation (membrane type 1-matrix metalloproteinase ablation) were compatible with development and survival. Their combined deficits, however, synergized to cause postnatal death by severely impairing bone formation. Interestingly, this was mechanistically linked to the proliferative failure and poor survival of cartilage- and bone-forming cells within their collagen-rich microenvironment. These findings have important implications for the use of pharmacological inhibitors of collagenase activity to prevent connective tissue destruction in a variety of diseases. |
Databáze: | OpenAIRE |
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