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Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein

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Abstract

Calcification of the extracellular matrix (ECM) can be physiological or pathological. Physiological calcification occurs in bone when the soft ECM is converted into a rigid material capable of sustaining mechanical force; pathological calcification can occur in arteries1 and cartilage2 and other soft tissues. No molecular determinant regulating ECM calcification has yet been identified. A candidate molecule is matrix GLA protein (Mgp), a mineral-binding ECM protein3 synthesized by vascular smooth-muscle cells and chondrocytes, two cell types that produce an uncalcified ECM. Mice that lack Mgp develop to term but die within two months as a result of arterial calcification which leads to bloodvessel rupture. Chondrocytes that elaborate a typical cartilage matrix can be seen in the affected arteries. Mgp-deficient mice additionally exhibit inappropriate calcification of various cartilages, including the growth plate, which eventually leads to short stature, osteopenia and fractures. These results indicate that ECM calcification must be actively inhibited in soft tissues. To our knowledge, Mgp is the first inhibitor of calcification of arteries and cartilage to be characterized in vivo.

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Author notes

  1. Marc D. McKee: Department of Stomatology, Faculty of Dentistry, Université de Montréal, Montréal, Quebec H3C 3J7, Canada

  2. Gerald J. Pinero: Department of Basic Science, Dental Branch-University of Texas, Houston, Texas 77030, USA

Authors and Affiliations

  1. Departments of Molecular Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, 77030, USA

    Guangbin Luo, Patricia Ducy, Richard R. Behringer & Gérard Karsenty

  2. Departments of Radiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, 77030, USA

    Evelyne Loyer

Authors
  1. Guangbin Luo
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  2. Patricia Ducy
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  3. Marc D. McKee
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  4. Gerald J. Pinero
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  5. Evelyne Loyer
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  6. Richard R. Behringer
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  7. Gérard Karsenty
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Luo, G., Ducy, P., McKee, M. et al. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 386, 78–81 (1997). https://doi.org/10.1038/386078a0

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