Vascular endothelial growth factor stimulates osteoblastic differentiation of cultured human periosteal-derived cells expressing vascular endothelial growth factor receptors.
Angiogenesis plays an important role in bone development and postnatal bone fracture repair. Vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptors (VEGFRs) are primarily involved in angiogenesis. This study investigated the expression of VEGF isoforms, VEGFR-1, and VEGFR-2 during the osteoblastic differentiation of cultured human periosteal-derived cells. In addition, the effect of exogenous VEGF on the osteoblastic differentiation of cultured human periosteal-derived cells was also examined. The expression of the VEGF isoforms (VEGF(121), VEGF(165), VEGF(189), and VEGF(206)), VEGFR-1, and VEGFR-2 was observed in the periosteal-derived cells. Administration of KRN633, a VEGFR-1 and VEGFR-2 inhibitor, decreased the alkaline phosphatase (ALP) activity during the osteoblastic differentiation of cultured human periosteal-derived cells. However, the administration of VEGFR2 Kinase Inhibitor IV, a VEGFR-2 inhibitor, did not affect the ALP activity. The addition of recombinant human VEGF(165) elevated the ALP activity and increased the calcium content in the periosteal-derived cells. Treating the periosteal-derived cells with recombinant human VEGF(165) resulted in an increase in Runx2 transactivation in the periosteal-derived cells. These results suggest that exogenous VEGF stimulates the osteoblastic differentiation of cultured human periosteal-derived cells and VEGF might act as an autocrine growth factor for the osteoblastic differentiation of cultured human periosteal-derived cells.
Hah
Young-Sool
YS
Clinical Research Institutue of Gyeongsang National University Hospital, Jinju, Republic of Korea.
Jun
Jin-Su
JS
Lee
Seong-Gyun
SG
Park
Bong-Wook
BW
Kim
Deok Ryong
DR
Kim
Uk-Kyu
UK
Kim
Jong-Ryoul
JR
Byun
June-Ho
JH
D000469:Alkaline Phosphatase / Q000378:metabolism; D002454:Cell Differentiation; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D006801:Humans; D010006:Osteoblasts / Q000166:cytology*; D010521:Periosteum / Q000166:cytology*; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
D050659:Core Binding Factor Alpha 1 Subunit; D020033:Protein Isoforms; D012333:RNA, Messenger; C493709:RUNX2 protein, human; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D000469:Alkaline Phosphatase