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

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

  2. Author Address

    Birkedal-Hansen H Natl Inst Dent & Craniofacial Res, MMP Unit Bethesda, MD 20892 USA Natl Inst Dent & Craniofacial Res, MMP Unit Bethesda, MD 20892 USA Univ Rome La Sapienza I-00161 Rome Italy Univ Aquila I-67100 Laquila Italy McGill Univ, Shriners Hosp Children, Canadian Unit, Joint Dis Lab Montreal PQ H3G 1A6 Canada NCI, Vet & Tumor Pathol Sect, Anim Sci Branch, Div Basic Sci Frederick, MD 21702 USA
    1. Year: 1999
  2. Journal: Cell
    1. 99
    2. 1
    3. Pages: 81-92
  4. Type of Article: Article
  1. 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. [References: 53]

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