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

被引：1036

作者：

Holmbeck, K

Bianco, P

Caterina, J

Yamada, S

Kromer, M

Kuznetsov, SA

Mankani, M

Robey, PG

Poole, AR

Pidoux, I

Ward, JM

Birkedal-Hansen, H ^{[1
]}

机构：

[1] Natl Inst Dent & Craniofacial Res, MMP Unit, Bethesda, MD 20892 USA

[2] Univ Roma La Sapienza, I-00161 Rome, Italy

[3] Univ Aquila, I-67100 Laquila, Italy

[4] McGill Univ, Shriners Hosp Children, Canadian Unit, Joint Dis Lab, Montreal, PQ H3G 1A6, Canada

[5] NCI, Vet & Tumor Pathol Sect, Anim Sci Branch, Div Basic Sci, Frederick, MD 21702 USA

来源：

CELL | 1999年 / 99卷 / 01期

关键词：

D O I：

10.1016/S0092-8674(00)80064-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：81 / 92

页数：12

共 55 条

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