Modulation of VEGF expression in rat bone marrow stromal cells by GDF-5.
Angiogenesis is essential for bone formation and several bone morphogenetic proteins (BMPs) have been shown to induce angiogenesis through osteoblast-derived vascular endothelial growth factor (VEGF)-A. Growth differentiation factor-5 (GDF-5) is a member of the BMP family expressed in bone and known to induce angiogenesis in vivo. In this study, the effects of GDF-5 on osteogenic differentiation and expression of VEGF-related genes were determined using rat bone marrow stromal cells. GDF-5 stimulated osteogenic differentiation. It also upregulated the expression of VEGF-A after 3 hr, accompanied by a trend of decrease in its receptor VEGFR-2 at 6 and 24 hr. VEGF-D and its receptor VEGFR-3 showed peak expression at later time points. This regulation may be further controlled by neuropilin 2 that exhibited a parallel profile to VEGF-D. These observations indicate that GDF-5 stimulates osteogenic differentiation and has a potential to induce angiogenesis through osteoblast-derived VEGF-A in bone.
Sena
Kotaro
K
Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, Illinois 60612, USA. Kotaro Sena@rush.edu
Sumner
Dale R
DR
Virdi
Amarjit S
AS
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D055428:Growth Differentiation Factor 5; D008297:Male; D010012:Osteogenesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000378:metabolism*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis
D019485:Bone Morphogenetic Proteins; D055428:Growth Differentiation Factor 5; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D003609:Dactinomycin; D003513:Cycloheximide; D040301:Vascular Endothelial Growth Factor Receptor-2