Rapid growth of cartilage rudiments may generate perichondrial structures by mechanical induction.

Experimental and theoretical research suggest that mechanical stimuli may play a role in morphogenesis. We investigated whether theoretically predicted patterns of stress and strain generated during the growth of a skeletal condensation are similar to in vivo expression patterns of chondrogenic and osteogenic genes. The analysis showed that predicted patterns of compressive hydrostatic stress (pressure) correspond to the expression patterns of chondrogenic genes, and predicted patterns of tensile strain correspond to the expression patterns of osteogenic genes. Furthermore, the results of iterative application of the analysis suggest that stresses and strains generated by the growing condensation could promote the formation and refinement of stiff tissue surrounding the condensation, a prediction that is in agreement with an observed increase in collagen bundling surrounding the cartilage condensation, as indicated by picro-sirius red staining. These results are consistent with mechanical stimuli playing an inductive or maintenance role in the developing cartilage and associated perichondrium and bone collar. This theoretical analysis provides insight into the potential importance of mechanical stimuli during the growth of skeletogenic condensations.

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 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.