MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover

K Holmbeck; P Bianco; J Caterina; S Yamada; M Kromer; S A Kuznetsov; M Mankani; P G Robey; A R Poole; I Pidoux; J M Ward; H Birkedal-Hansen

MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover

K Holmbeck, P Bianco, J Caterina, S Yamada, M Kromer, S A Kuznetsov, M Mankani, P G Robey, A R Poole, I Pidoux, J M Ward, H Birkedal-Hansen

1008 Citations (Scopus)

Abstract

MT1-MMP is a membrane-bound matrix metalloproteinase (MT-MMP) capable of mediating pericellular proteolysis of extracellular matrix components. MT1-MMP is therefore thought to be an important molecular tool for cellular remodeling of the surrounding matrix. To establish the biological role of this membrane proteinase we generated MT1-MMP-deficient mice by gene targeting. MT1-MMP deficiency causes craniofacial dysmorphism, arthritis, osteopenia, dwarfism, and fibrosis of soft tissues due to ablation of a collagenolytic activity that is essential for modeling of skeletal and extraskeletal connective tissues. Our findings demonstrate the pivotal function of MT1-MMP in connective tissue metabolism, and illustrate that modeling of the soft connective tissue matrix by resident cells is essential for the development and maintenance of the hard tissues of the skeleton.

Original language	English
Journal	Cell
Volume	99
Issue number	1
Pages (from-to)	81-92
Number of pages	12
ISSN	0092-8674
Publication status	Published - 1 Oct 1999

Keywords

Animals
Arthritis/genetics
Body Constitution
Bone Development
Bone Diseases, Metabolic/genetics
Bone Resorption/pathology
Cachexia/genetics
Cartilage/pathology
Collagen/metabolism
Connective Tissue Diseases/genetics
Disease Models, Animal
Dwarfism/genetics
Fibrosis
Growth Plate/pathology
Hyalin
Matrix Metalloproteinase 14
Matrix Metalloproteinases/genetics
Matrix Metalloproteinases, Membrane-Associated
Metalloendopeptidases
Mice
Mice, Knockout
Osteoblasts/enzymology
Skin/cytology
Skull/pathology
Stromal Cells/pathology
Synovial Membrane/pathology

Cite this

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title = "MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover",

abstract = "MT1-MMP is a membrane-bound matrix metalloproteinase (MT-MMP) capable of mediating pericellular proteolysis of extracellular matrix components. MT1-MMP is therefore thought to be an important molecular tool for cellular remodeling of the surrounding matrix. To establish the biological role of this membrane proteinase we generated MT1-MMP-deficient mice by gene targeting. MT1-MMP deficiency causes craniofacial dysmorphism, arthritis, osteopenia, dwarfism, and fibrosis of soft tissues due to ablation of a collagenolytic activity that is essential for modeling of skeletal and extraskeletal connective tissues. Our findings demonstrate the pivotal function of MT1-MMP in connective tissue metabolism, and illustrate that modeling of the soft connective tissue matrix by resident cells is essential for the development and maintenance of the hard tissues of the skeleton.",

keywords = "Animals, Arthritis/genetics, Body Constitution, Bone Development, Bone Diseases, Metabolic/genetics, Bone Resorption/pathology, Cachexia/genetics, Cartilage/pathology, Collagen/metabolism, Connective Tissue Diseases/genetics, Disease Models, Animal, Dwarfism/genetics, Fibrosis, Growth Plate/pathology, Hyalin, Matrix Metalloproteinase 14, Matrix Metalloproteinases/genetics, Matrix Metalloproteinases, Membrane-Associated, Metalloendopeptidases, Mice, Mice, Knockout, Osteoblasts/enzymology, Skin/cytology, Skull/pathology, Stromal Cells/pathology, Synovial Membrane/pathology",

author = "K Holmbeck and P Bianco and J Caterina and S Yamada and M Kromer and Kuznetsov, {S A} and M Mankani and Robey, {P G} and Poole, {A R} and I Pidoux and Ward, {J M} and H Birkedal-Hansen",

year = "1999",

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language = "English",

volume = "99",

pages = "81--92",

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T1 - MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover

AU - Holmbeck, K

AU - Bianco, P

AU - Caterina, J

AU - Yamada, S

AU - Kromer, M

AU - Kuznetsov, S A

AU - Mankani, M

AU - Robey, P G

AU - Poole, A R

AU - Pidoux, I

AU - Ward, J M

AU - Birkedal-Hansen, H

PY - 1999/10/1

Y1 - 1999/10/1

N2 - MT1-MMP is a membrane-bound matrix metalloproteinase (MT-MMP) capable of mediating pericellular proteolysis of extracellular matrix components. MT1-MMP is therefore thought to be an important molecular tool for cellular remodeling of the surrounding matrix. To establish the biological role of this membrane proteinase we generated MT1-MMP-deficient mice by gene targeting. MT1-MMP deficiency causes craniofacial dysmorphism, arthritis, osteopenia, dwarfism, and fibrosis of soft tissues due to ablation of a collagenolytic activity that is essential for modeling of skeletal and extraskeletal connective tissues. Our findings demonstrate the pivotal function of MT1-MMP in connective tissue metabolism, and illustrate that modeling of the soft connective tissue matrix by resident cells is essential for the development and maintenance of the hard tissues of the skeleton.

AB - MT1-MMP is a membrane-bound matrix metalloproteinase (MT-MMP) capable of mediating pericellular proteolysis of extracellular matrix components. MT1-MMP is therefore thought to be an important molecular tool for cellular remodeling of the surrounding matrix. To establish the biological role of this membrane proteinase we generated MT1-MMP-deficient mice by gene targeting. MT1-MMP deficiency causes craniofacial dysmorphism, arthritis, osteopenia, dwarfism, and fibrosis of soft tissues due to ablation of a collagenolytic activity that is essential for modeling of skeletal and extraskeletal connective tissues. Our findings demonstrate the pivotal function of MT1-MMP in connective tissue metabolism, and illustrate that modeling of the soft connective tissue matrix by resident cells is essential for the development and maintenance of the hard tissues of the skeleton.

KW - Animals

KW - Arthritis/genetics

KW - Body Constitution

KW - Bone Development

KW - Bone Diseases, Metabolic/genetics

KW - Bone Resorption/pathology

KW - Cachexia/genetics

KW - Cartilage/pathology

KW - Collagen/metabolism

KW - Connective Tissue Diseases/genetics

KW - Disease Models, Animal

KW - Dwarfism/genetics

KW - Fibrosis

KW - Growth Plate/pathology

KW - Hyalin

KW - Matrix Metalloproteinase 14

KW - Matrix Metalloproteinases/genetics

KW - Matrix Metalloproteinases, Membrane-Associated

KW - Metalloendopeptidases

KW - Mice

KW - Mice, Knockout

KW - Osteoblasts/enzymology

KW - Skin/cytology

KW - Skull/pathology

KW - Stromal Cells/pathology

KW - Synovial Membrane/pathology

M3 - Journal article

C2 - 10520996

SN - 0092-8674

VL - 99

SP - 81

EP - 92

JO - Cell

JF - Cell

IS - 1

ER -

MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover

Abstract

Keywords

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