VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation
VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation
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DOI：
10.1038/9467
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发表时间：
1999-06-01
期刊：
影响因子：
82.9
通讯作者：
Ferrara, N
中科院分区：
文献类型：
--
作者：
Gerber, HP;Vu, TH;Ferrara, N
骺生长板中的肥大软骨细胞表达血管生成蛋白血管内皮生长因子（VEGF）。为了确定VECF在软骨内骨形成中的作用，我们通过对24日龄小鼠全身给予可溶性受体嵌合蛋白（Flt-（1-3）-IgG）来灭活该因子。血管侵袭几乎完全被抑制，伴随着骨小梁形成受损和肥大软骨细胞区扩张。表达明胶酶B/基质金属蛋白酶9的破软骨细胞的募集和/或分化以及终末软骨细胞的吸收减少。软骨细胞增殖、分化、成熟正常，但骨吸收受到抑制。停止抗VEGF治疗后，毛细血管浸润，骨生长恢复，肥大软骨吸收和生长板结构正常化。这些发现表明VEGF介导的毛细血管侵入是调节生长板形态发生和触发软骨重塑的重要信号。因此，VECF是软骨细胞死亡、破软骨细胞功能、细胞外基质重塑、血管生成和生长板中骨形成的重要协调者。
Hypertrophic chondrocytes in the epiphyseal growth plate express the angiogenic protein vascular endothelial growth factor (VEGF). To determine the role of VECF in endochondral bone formation, we inactivated this factor through the systemic administration of a soluble receptor chimeric protein (Flt-(1-3)-IgG) to 24-day-old mice. Blood vessel invasion was almost completely suppressed, concomitant with impaired trabecular bone formation and expansion of hypertrophic chondrocyte zone. Recruitment and/or differentiation of chondroclasts, which express gelatinase B/matrix metalloproteinase-9, and resorption of terminal chondrocytes decreased. Although proliferation, differentiation and maturation of chondrocytes were apparently normal, resorption was inhibited. Cessation of the anti-VEGF treatment was followed by capillary invasion, restoration of bone growth, resorption of the hypertrophic cartilage and normalization of the growth plate architecture. These findings indicate that VEGF-mediated capillary invasion is an essential signal that regulates growth plate morphogenesis and triggers cartilage remodeling. Thus, VECF is an essential coordinator of chandrocyte death, chondroclast function, extracellular matrix remodeling, angiogenesis and bone formation in the growth plate.