| Bone formation by endochondral ossification is traditionally viewed as a process in which only cells of the osteo and chondral lineages are involved. New studies have shown that the vasculature, which is critical to the growth and survival of all organ systems, and provides critical developmental signals for cartilage and bone tissue.; The skeletogenic mesenchyme undergoes various states of vascularization during development from mesenchyme to long bone. In the embryonic chick limb, uncommitted, vascularized mesenchyme becomes avascular through active vascular regression, leaving a prechondrogenic mesenchymal field. This avascular mesenchyme condenses and commits to the chondrogenic lineage. We found that inhibition of the vascular regression process inhibits condensation of precartilaginous mesenchyme, indicating a requirement of avascularity for cartilage differentiation.; This avascular state, characteristic of cartilage, is reversed during the process of endochondral ossification within the long bone. Blood vessels bring necessary signals and cells for proper terminal differentiation of chondrocytes and bone formation. We perturbed the vascular system of the elongating humerus with the antiangiogenic compound squalamine and found that proper vascularization is required for ossification. Surprisingly, we also uncovered a need for blood vessels in stimulating earlier stages of chondrocyte maturation, despite the cartilage remaining avascular.; Our findings highlight the complex communication between vastly different tissues in the skeletal and circulatory systems. Our studies will stimulate more research into this new form of epithelial-mesenchymal interaction, which we believe will prove increasingly important in developmental biology. |
