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

The replacement of cartilage by bone is the net result of genetic programs that control chondrocyte differentiation, matrix degradation, and bone form ation. Disruptions in the rate, timing, or duration of chondrocyte prolifer ation and differentiation result in shortened, misshapen skeletal elements. In the majority of these skeletal disruptions, vascular invasion of the el ements 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 vascular ization of the developing skeleton that provides a framework in which to in terpret a wide range of fetal skeletal malformations, disruptions, and dysp lasias. (C) 2001 Elsevier Science Ireland Ltd. AII rights reserved.