Yao Zhenqiang, Lafage-Proust Marie-Hélène, Plouët Jean, Bloomfield Susan, Alexandre Christian, Vico Laurence
Faculté de Médecine, Laboratoire de Biologie du Tissu Osseux, Saint-Etienne Cedex 02 42023, France.
J Bone Miner Res. 2004 Sep;19(9):1471-80. doi: 10.1359/JBMR.040517. Epub 2004 Jun 2.
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.
We investigated the role of vascular endothelial growth factor (VEGF) and angiogenesis in the osteogenic response to exercise.
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.
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.
VEGF signaling-mediated bone angiogenesis is tightly related to exercise-induced bone cellular uncoupling and is indispensable for bone gain induced by exercise.
骨重塑过程中的生理性血管生成尚不清楚。跑步机跑步的大鼠显示骨髓血管生成，同时胫骨近端骨形成增加、吸收减少，以及VEGF及其R1受体mRNA上调。在5周的训练期间进行VEGF阻断可完全阻止运动诱导的骨量增加。
我们研究了血管内皮生长因子（VEGF）和血管生成在运动对成骨反应中的作用。
9周龄雄性Wistar大鼠在60%最大摄氧量（Vo₂max）下进行不同时间段的跑步机训练。在2周和5周实验后进行骨和血管组织形态计量学分析。在10天实验后进行VEGF及其受体R1和R2的在线逆转录聚合酶链反应（RT PCR）。在5周实验中，跑步大鼠接受VEGF抑制抗体或安慰剂。
2周后，胫骨骨密度未改变；然而，与久坐大鼠相比，跑步大鼠近端干骺端的血管数量增加了20%。在跑步大鼠中，血管数量与骨形成率呈正相关（r = 0.88），与活跃吸收表面呈负相关（r = -0.85）。训练10天后，在骨膜和干骺端骨中检测到VEGF和VEGF受体R1 mRNA上调。在5周训练的大鼠中进行VEGF阻断可完全阻止运动诱导的干骺端骨密度增加（9%）和松质骨体积增加（骨体积/总体积；25%），以及血管数量增加（25%）。在5周接受安慰剂治疗的跑步大鼠中，骨形成率恢复到初始值，而与久坐和接受抗VEGF治疗的跑步大鼠相比，破骨细胞表面继续下降。
VEGF信号介导的骨血管生成与运动诱导的骨细胞解偶联密切相关，并且对于运动诱导的骨量增加是必不可少的。
