ECTS2014 Workshops Blood supply in pathophysiology of bone (3 abstracts)
Saint-Etienne, France.
Blood vessels and bone display spatial and functional relationships. While the coupling of angiogenesis to bone formation during modeling situations is well documented, the vessels roles in bone remodeling, although widely acknowledged, remain poorly explored. In order to image and quantify the bone vessel network in rodents, we contrasted the vascular bed with barium sulfate, followed by histology or either conventional or synchrotron radiation micro-computed tomography. We showed that treadmill running induces angiogenesis in the rat while unloading decreases bone vessel density. Further, blocking vessel development with anti-VEGF-antibody prevented physical exercise-induced bone gain. Conversely, intermittent PTH1-84 (iPTH) administration, although osteoanabolic, was not associated with bone angiogenesis. However, image quantitative analysis revealed that PTH affects the smallest vessels by relocating them closer to bone-forming sites. At that point, our next aim was to analyse bone vessels at both structural and functional levels and we turned to the mouse model. We found that tibia perfusion, evaluated by Laser Doppler, as well as vessel density, declined after ovariectomy prior to bone loss. We then compared iPTH to continuous PTH at the same daily doses, which both stimulate bone formation regardless of administration mode. iPTH increased vessel size and bone perfusion while cPTH did not. Thus, angiogenesis and bone formation in anabolic situations are not always coupled and challenge-induced variations of vessel density and bone perfusion do not necessarily point in the same direction. We hypothesize that a post-angiogenesis process may be involved in the bone-vessel crosstalk whose deciphering will need further technical developments