RGD Reference Report - Increase of both angiogenesis and bone mass in response to exercise depends on VEGF. - Rat Genome Database

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Increase of both angiogenesis and bone mass in response to exercise depends on VEGF.

Authors: Yao, Z  Lafage-Proust, MH  Plouet, J  Bloomfield, S  Alexandre, C  Vico, L 
Citation: Yao Z, etal., J Bone Miner Res. 2004 Sep;19(9):1471-80. Epub 2004 Jun 2.
RGD ID: 1580559
Pubmed: PMID:15312247   (View Abstract at PubMed)
DOI: DOI:10.1359/JBMR.040517   (Journal Full-text)

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.

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Vegfa  (vascular endothelial growth factor A)

Additional Information