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 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Cell
Vol/bind	99
Udgave nummer	1
Sider (fra-til)	81-92
Antal sider	12
ISSN	0092-8674
Status	Udgivet - 1 okt. 1999

Citationsformater

@article{d3108c5f077141048f5ccb8788bbefbc,

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",

month = oct,

day = "1",

language = "English",

volume = "99",

pages = "81--92",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "1",

}

TY - JOUR

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

Fingeraftryk

Citationsformater