Spontaneous Calcification of Arteries and Cartilage in Mice Lacking Matrix GLA Protein

Nature. 1997 Mar 6;386(6620):78-81. doi: 10.1038/386078a0.

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 arteries and cartilage 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 protein 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 blood-vessel 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Aorta, Abdominal / metabolism
  • Aorta, Abdominal / ultrastructure
  • Arteries / embryology
  • Arteries / metabolism
  • Arteries / ultrastructure
  • Calcinosis / embryology
  • Calcinosis / etiology*
  • Calcinosis / metabolism
  • Calcium-Binding Proteins / deficiency*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / physiology
  • Cartilage / embryology
  • Cartilage / metabolism
  • Cartilage / ultrastructure
  • Cartilage Diseases / etiology*
  • Cartilage Diseases / mortality
  • Cartilage Diseases / pathology
  • Extracellular Matrix Proteins / deficiency*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / physiology
  • Female
  • Gene Targeting
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Stem Cells
  • Vascular Diseases / etiology*
  • Vascular Diseases / mortality
  • Vascular Diseases / pathology

Substances

  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • matrix Gla protein