VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation.
Nat Med
; 5(6): 623-8, 1999 Jun.
Article
em En
| MEDLINE
| ID: mdl-10371499
ABSTRACT
Hypertrophic chondrocytes in the epiphyseal growth plate express the angiogenic protein vascular endothelial growth factor (VEGF). To determine the role of VEGF 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, VEGF is an essential coordinator of chondrocyte death, chondroclast function, extracellular matrix remodeling, angiogenesis and bone formation in the growth plate.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteogênese
/
Osso e Ossos
/
Cartilagem
/
Fatores de Crescimento Endotelial
/
Linfocinas
/
Neovascularização Fisiológica
/
Condrócitos
Limite:
Animals
Idioma:
En
Revista:
Nat Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos