Bone formation during distraction osteogenesis is dependent on both VEGFR1 and VEGFR2 signaling.
J Bone Miner Res
; 23(5): 596-609, 2008 May.
Article
en En
| MEDLINE
| ID: mdl-18433297
INTRODUCTION: Distraction osteogenesis (DO) is characterized by the induction of highly vascularized new bone formation through an intramembranous process largely devoid of the formation of cartilage. MATERIALS AND METHODS: To test the hypothesis that DO is strictly dependent on vascualrization, we inhibited vascular endothelial growth factor (VEGF) activity by antibody blockade of both receptors VEGFR1 (Flt-1) and VEGFR2 (Flk-1) or only VEGFR2 (Flk-1) in a previously developed murine tibia DO model. During normal DO, VEGFR1 (Flt-1), VEGFR2 (Flk-1), VEGFR3 (Flt4) and all four VEGF ligand (A, B, C, and D) mRNAs are induced. RESULTS: The expression of mRNA for the receptors generally paralleled those of the ligands during the period of active distraction. Bone formation, as assessed by muCT, showed a significant decrease with the double antibody treatment and a smaller decrease with single antibody treatment. Vessel volume, number, and connectivity showed progressive and significant inhibition in all of these of parameters between the single and double antibody blockade. Molecular analysis showed significant inhibition in skeletal cell development with the single and double antibody blockade of both VEGFR1 and 2. Interestingly, the single antibody treatment led to selective early development of chondrogenesis, whereas the double antibody treatment led to a failure of both osteogenesis and chondrogenesis. CONCLUSIONS: Both VEGFR1 and VEGFR2 are functionally essential in blood vessel and bone formation during DO and are needed to promote osteogenic over chondrogenic lineage progression.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Desarrollo Óseo
/
Transducción de Señal
/
Receptor 1 de Factores de Crecimiento Endotelial Vascular
/
Receptor 2 de Factores de Crecimiento Endotelial Vascular
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Bone Miner Res
Asunto de la revista:
METABOLISMO
/
ORTOPEDIA
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos