VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation

被引:1601
作者
Gerber, HP
Vu, TH
Ryan, AM
Kowalski, J
Werb, Z
Ferrara, N
机构
[1] Genentech Inc, Dept Cardiovasc Res, S San Francisco, CA 94080 USA
[2] Genentech Inc, Dept Pathol, S San Francisco, CA 94080 USA
[3] Univ Calif San Francisco, Med Ctr, Dept Anat, San Francisco, CA 94143 USA
关键词
D O I
10.1038/9467
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:623 / 628
页数:6
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