On the role of MT1-MMP, a matrix metalloproteinase essential to collagen remodeling, in murine molar eruption and root growth

TY - JOUR

T1 - On the role of MT1-MMP, a matrix metalloproteinase essential to collagen remodeling, in murine molar eruption and root growth

AU - Beertsen, Wouter

AU - Holmbeck, Kenn

AU - Niehof, Anneke

AU - Bianco, Paolo

AU - Chrysovergis, Kaliiopi

AU - Birkedal-Hansen, Henning

AU - Everts, Vincent

PY - 2002/12

Y1 - 2002/12

N2 - 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.

AB - 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.

KW - Animals

KW - Fibrillar Collagens/metabolism

KW - Fibroblasts/enzymology

KW - Matrix Metalloproteinase 14

KW - Matrix Metalloproteinases, Membrane-Associated

KW - Metalloendopeptidases/physiology

KW - Mice

KW - Mice, Mutant Strains

KW - Molar/enzymology

KW - Periodontal Ligament/cytology

KW - Phagosomes/ultrastructure

KW - Tooth Eruption/physiology

KW - Tooth Root/enzymology

M3 - Journal article

C2 - 12507218

SN - 0909-8836

VL - 110

SP - 445

EP - 451

JO - European Journal of Oral Sciences

JF - European Journal of Oral Sciences

IS - 6

ER -