On the role of MT1-MMP, a matrix metalloproteinase essential to collagen remodeling, in murine molar eruption and root growth.
Although the connective tissues of the periodontium are subject to a high turnover rate, no conclusive evidence has yet emerged that periodontal collagen turnover is essential for the eruption of teeth or for root elongation. These processes were studied in mice deficient in MT1-MMP, a membrane type matrix metalloproteinase essential for remodeling of soft tissue-hard tissue interfaces. Mandibular first molars of deficient mice and their wild-type littermates were subjected to stereological analysis in order to assess root length, eruption and the volume density of phagocytosed collagen in periodontal ligament fibroblasts. The data showed that both eruption and root elongation were severely inhibited in animals lacking the enzyme. We also found, in periodontal ligament fibroblasts from MT1-MMP-deficient mice, a massive age-related accumulation (up to 60-fold over controls) of collagen fibril-containing phagosomes. Phagolysosomes, which represent the next downstream step in collagen fibril degradation by the lysosomal pathway, did not accumulate. These observations indicate that MT1-MMP plays a central role in periodontal remodeling. The stunted root growth and the failure to erupt indicate the important role of the enzyme in tooth development.
Beertsen
Wouter
W
Department of Periodontology, Academic Center for Dentistry Amsterdam, University of Amsterdam, The Netherlands. w.beertsen@acta.nl
Holmbeck
Kenn
K
Niehof
Anneke
A
Bianco
Paolo
P
Chrysovergis
Kaliiopi
K
Birkedal-Hansen
Henning
H
Everts
Vincent
V
D000818:Animals; D024022:Fibrillar Collagens / Q000378:metabolism*; D005347:Fibroblasts / Q000201:enzymology; D053511:Matrix Metalloproteinase 14; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D008963:Molar / Q000201:enzymology / Q000254:growth & development; D010513:Periodontal Ligament / Q000166:cytology / Q000201:enzymology*; D010588:Phagosomes / Q000648:ultrastructure; D014078:Tooth Eruption / Q000502:physiology*; D014092:Tooth Root / Q000201:enzymology* / Q000254:growth & development*
D024022:Fibrillar Collagens; C507096:Mmp14 protein, mouse; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D053511:Matrix Metalloproteinase 14