MT1-MMP and type II collagen specify skeletal stem cells and their bone and cartilage progeny

Ludmila Szabova, Susan S Yamada, Helen Wimer, Kaliopi Chrysovergis, Signe Ingvarsen, Niels Behrendt, Lars H Engelholm, Kenn Holmbeck

    29 Citations (Scopus)

    Abstract

    Skeletal formation is dependent on timely recruitment of skeletal stem cells and their ensuing synthesis and remodeling of the major fibrillar collagens, type I collagen and type II collagen, in bone and cartilage tissues during development and postnatal growth. Loss of the major collagenolytic activity associated with the membrane-type 1 matrix metalloproteinase (MT1-MMP) results in disrupted skeletal development and growth in both cartilage and bone, where MT1-MMP is required for pericellular collagen dissolution. We show here that reconstitution of MT1-MMP activity in the type II collagen-expressing cells of the skeleton rescues not only diminished chondrocyte proliferation, but surprisingly, also results in amelioration of the severe skeletal dysplasia associated with MT1-MMP deficiency through enhanced bone formation. Consistent with this increased bone formation, type II collagen was identified in bone cells and skeletal stem/progenitor cells of wildtype mice. Moreover, bone marrow stromal cells isolated from mice expressing MT1-MMP under the control of the type II collagen promoter in an MT1-MMP-deficient background showed enhanced bone formation in vitro and in vivo compared with cells derived from nontransgenic MT1-MMP-deficient littermates. These observations show that type II collagen is not stringently confined to the chondrocyte but is expressed in skeletal stem/progenitor cells (able to regenerate bone, cartilage, myelosupportive stroma, marrow adipocytes) and in the chondrogenic and osteogenic lineage progeny where collagenolytic activity is a requisite for proper cell and tissue function.
    Original languageEnglish
    JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
    Volume24
    Issue number11
    Pages (from-to)1905-16
    Number of pages12
    ISSN0884-0431
    DOIs
    Publication statusPublished - Nov 2009

    Keywords

    • Adipocytes
    • Animals
    • Body Weight
    • Bone Marrow
    • Bone and Bones
    • Cartilage
    • Cell Lineage
    • Cell Proliferation
    • Chondrocytes
    • Collagen Type II
    • Matrix Metalloproteinase 14
    • Mice
    • Organ Specificity
    • Osteogenesis
    • Rats
    • Stem Cells
    • Survival Analysis
    • Transgenes
    • Weight Gain

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