血管内皮细胞缺失ADAM10通过干扰Notch信号通路诱导血管过度侵袭生长及骨骺早期闭合研究

ADAM10 depletion of vascular endothelial cells induced excessive vascular invasion and growth and early closure of epiphyses by interfering with Notch signaling pathway

目的探讨血管内皮细胞缺失ADAM10(ADAM10ΔEC)严重影响股骨生长的原因以及ADAM10ΔEC干扰血管新生的机制。方法对ADAM10ΔEC小鼠与对照小鼠股骨行阿辛蓝与茜素红大体骨-软骨染色,对其组织切片行HE染色与番红O-固绿染色,并行内皮黏蛋白荧光染色血管内皮细胞,抗酒石酸酸性磷酸酶染色破骨细胞,以及凋亡细胞荧光染色。结果骨骺提前闭合只出现在ADAM10ΔEC股骨中,并开始于肥大软骨细胞侵入并穿过生长板,血管的过度侵入,以及破骨细胞的浸润,最终形成局灶性生长板中断,细胞凋亡参与该重塑进程。ADAM10在内皮细胞中的失活可能会影响Notch信号参与的血管生成。结论 Notch信号在软骨内骨化的血管侵入中具有关键作用。

Objective To investigate the cause of ADAM10 depletion of vascular endothelial cells(ADAM10ΔEC) seriously affecting the growth of femur and the mechanism of ADAM10ΔEC interfering with angiogenesis.Methods The femurs of ADAM10ΔEC mice and control mice were stained with alcian blue and alizarin red.The sections of the femurs were stained with HE,Safranine 0-fixation green.The endothelial cells,osteoclasts and apoptotic cells were stained with fluorescence.Results Epiphyseal closed only appear in early ADAM10ΔEC in the femur,and start in hypertrophy of cartilage cells into and through the growth plate,excessive blood vessel invasion,infiltration and osteoclast,eventually form a focal growth plate,apoptosis to participate in the reshaping process.The inactivation of ADAM10 in endothelial cells may affect the angiogenesis involved in Notch signaling.Conclusion Notch signaling plays a key role in the vascular invasion of endochondral ossification.