Increase of both angiogenesis and bone mass in response to exercise depends on VEGF. Academic Article uri icon

abstract

  • UNLABELLED: Physiological angiogenesis during bone remodeling is undefined. Treadmill-running rats displayed bone marrow angiogenesis concomitant with bone formation increase and resorption decrease and upregulation of VEGF and its R1 receptor mRNA in proximal tibia. VEGF blockade over 5 weeks of training fully prevented the exercise-induced bone mass gain. INTRODUCTION: We investigated the role of vascular endothelial growth factor (VEGF) and angiogenesis in the osteogenic response to exercise. MATERIALS AND METHODS: Nine-week-old male Wistar rats were treadmill-trained at 60% Vo(2max) for various periods. Bone and vascular histomorphometry was performed after 2- and 5-week experiments. On-line RT PCR for VEGF and its receptors R1 and R2 was done after a 10-day experiment. In the 5-week experiment, running rats received either a VEGF inhibitory antibody or a placebo. RESULTS: After 2 weeks, tibial BMD did not change; however, vessel number in the proximal metaphysis increased by 20% in running versus sedentary rats. In running rats, vessel number correlated positively (r = 0.88) with bone formation rate and negatively (r = -0.85) with active resorption surfaces. After 10 days of training, upregulation of VEGF and VEGF receptor R1 mRNA was detected in periosteum and metaphyseal bone. VEGF blockade in 5-week trained rats fully prevented the exercise-induced increase in metaphyseal BMD (9%) and cancellous bone volume (BV/TV; 25%), as well as the increased vessel number (25%). In 5-week placebo-treated running rats, bone formation rate returned to initial values, whereas osteoclastic surfaces continued to decline compared with both sedentary and anti-VEGF-treated running rats. CONCLUSION: VEGF signaling-mediated bone angiogenesis is tightly related to exercise-induced bone cellular uncoupling and is indispensable for bone gain induced by exercise.

published proceedings

  • J Bone Miner Res

author list (cited authors)

  • Yao, Z., Lafage-Proust, M., Plout, J., Bloomfield, S., Alexandre, C., & Vico, L.

citation count

  • 94

complete list of authors

  • Yao, Zhenqiang||Lafage-Proust, Marie-Hélène||Plouët, Jean||Bloomfield, Susan||Alexandre, Christian||Vico, Laurence

publication date

  • September 2004

publisher