Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I

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  • Zhongjun Zhou
    Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden; Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation ND-20, 9500 Euclid Avenue, Cleveland, OH 44195; Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden; Glenn Research Center, Life Prediction Branch, National Aeronautics and Space Administration, Cleveland, OH 44135; and Department of Molecular...
  • Suneel S. Apte
    Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden; Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation ND-20, 9500 Euclid Avenue, Cleveland, OH 44195; Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden; Glenn Research Center, Life Prediction Branch, National Aeronautics and Space Administration, Cleveland, OH 44135; and Department of Molecular...
  • Raija Soininen
    Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden; Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation ND-20, 9500 Euclid Avenue, Cleveland, OH 44195; Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden; Glenn Research Center, Life Prediction Branch, National Aeronautics and Space Administration, Cleveland, OH 44135; and Department of Molecular...
  • Renhai Cao
    Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden; Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation ND-20, 9500 Euclid Avenue, Cleveland, OH 44195; Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden; Glenn Research Center, Life Prediction Branch, National Aeronautics and Space Administration, Cleveland, OH 44135; and Department of Molecular...
  • George Y. Baaklini
    Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden; Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation ND-20, 9500 Euclid Avenue, Cleveland, OH 44195; Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden; Glenn Research Center, Life Prediction Branch, National Aeronautics and Space Administration, Cleveland, OH 44135; and Department of Molecular...
  • Richard W. Rauser
    Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden; Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation ND-20, 9500 Euclid Avenue, Cleveland, OH 44195; Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden; Glenn Research Center, Life Prediction Branch, National Aeronautics and Space Administration, Cleveland, OH 44135; and Department of Molecular...
  • Jianming Wang
    Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden; Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation ND-20, 9500 Euclid Avenue, Cleveland, OH 44195; Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden; Glenn Research Center, Life Prediction Branch, National Aeronautics and Space Administration, Cleveland, OH 44135; and Department of Molecular...
  • Yihai Cao
    Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden; Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation ND-20, 9500 Euclid Avenue, Cleveland, OH 44195; Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden; Glenn Research Center, Life Prediction Branch, National Aeronautics and Space Administration, Cleveland, OH 44135; and Department of Molecular...
  • Karl Tryggvason
    Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden; Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation ND-20, 9500 Euclid Avenue, Cleveland, OH 44195; Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden; Glenn Research Center, Life Prediction Branch, National Aeronautics and Space Administration, Cleveland, OH 44135; and Department of Molecular...

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<jats:p> Membrane-type matrix metalloproteinase I (MT1-MMP)-deficient mice were found to have severe defects in skeletal development and angiogenesis. The craniofacial, axial, and appendicular skeletons were severely affected, leading to a short and domed skull, marked deceleration of postnatal growth, and death by 3 wk of age. Shortening of bones is a consequence of decreased chondrocyte proliferation in the proliferative zone of the growth plates. Defective vascular invasion of cartilage leads to enlargement of hypertrophic zones of growth plates and delayed formation of secondary ossification centers in long bones. In an <jats:italic>in vivo</jats:italic> corneal angiogenesis assay, null mice did not have angiogenic response to implanted FGF-2, suggesting that the defect in angiogenesis is not restricted to cartilage alone. In tissues from null mice, activation of latent matrix metalloproteinase 2 was deficient, suggesting that MT1-MMP is essential for its activation <jats:italic>in vivo</jats:italic> . </jats:p>

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