The authors have no conflict of interest
Increase of Both Angiogenesis and Bone Mass in Response to Exercise Depends on VEGF†
Article first published online: 2 JUN 2004
Copyright © 2004 ASBMR
Journal of Bone and Mineral Research
Volume 19, Issue 9, pages 1471–1480, September 2004
How to Cite
Yao, Z., Lafage-Proust, M.-H., Plouët, J., Bloomfield, S., Alexandre, C. and Vico, L. (2004), Increase of Both Angiogenesis and Bone Mass in Response to Exercise Depends on VEGF. J Bone Miner Res, 19: 1471–1480. doi: 10.1359/JBMR.040517
- Issue published online: 2 DEC 2009
- Article first published online: 2 JUN 2004
- Manuscript Accepted: 5 MAY 2004
- Manuscript Revised: 25 MAR 2004
- Manuscript Received: 17 FEB 2004
- bone and vascular histomorphometry;
- neutralizing vascular endothelial growth factor antibody;
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% VO2max 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.