A molecular analysis of matrix remodeling and angiogenesis during long bone development

Mech Dev. 2001 Feb;100(2):245-50. doi: 10.1016/s0925-4773(00)00532-3.


The replacement of cartilage by bone is the net result of genetic programs that control chondrocyte differentiation, matrix degradation, and bone formation. Disruptions in the rate, timing, or duration of chondrocyte proliferation and differentiation result in shortened, misshapen skeletal elements. In the majority of these skeletal disruptions, vascular invasion of the elements is also perturbed. Our hypothesis is that the processes involved in endochondral ossification are synchronized via the vasculature. The purpose of this study was to examine carefully the events of vascular invasion and matrix degradation in the context of chondrocyte differentiation and bone formation. Here, we have produced a 'molecular map' of the initial vascularization of the developing skeleton that provides a framework in which to interpret a wide range of fetal skeletal malformations, disruptions, and dysplasias.

Publication types

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

MeSH terms

  • Animals
  • Bone Development*
  • Bone Matrix / blood supply*
  • Bone Matrix / embryology*
  • Chondrocytes / cytology
  • Endothelial Growth Factors / biosynthesis
  • Extremities / embryology
  • Immunohistochemistry
  • In Situ Hybridization
  • In Situ Nick-End Labeling
  • Lymphokines / biosynthesis
  • Mice
  • Neovascularization, Physiologic*
  • Time Factors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors