VEGF and VEGF receptors are differentially expressed in chondrocytes.
During long bone development, cartilage replacement by bone is governed in part by angiogenesis. Although it has been demonstrated that vascular endothelial growth factor (VEGF-A) is crucial during endochondral ossification, little is known about the involvement of the other VEGF family members. Thus, we examined the expression and production of these members on primary chondrocytes and ATDC5 chondrogenic cells. VEGF-A, VEGF-B, VEGF-C and VEGF-D were shown to be expressed and synthesized demonstrating that numerous angiogenic factors can be produced by chondrocytes. In ATDC5 VEGF-A, VEGF-B and VEGF-C were over-expressed in the presence of chondrogenic and bone morphogenetic protein (BMP)-2 treatment suggesting that these factors play an important role during chondrogenesis. In addition, neuropilin-1, VEGF receptor-2 and VEGF receptor-3 gene expression were observed with an increase in VEGF-R2 expression under chondrogenic and BMP-2 treatment, suggesting that VEGF proteins could act in an autocrine/paracrine manner in addition to their angiogenic function. In conclusion, we demonstrated for the first time that chondrocytes secreted the four members of the VEGF family. We also showed that VEGF-B, VEGF-C and VEGF-D were secreted as processed proteins. The up-regulation of VEGF-B and VEGF-C at the mRNA and protein levels under chondrogenic stimulation strongly suggests a major role for these proteins in growth plate physiology.
Bluteau
Gilles
G
INSERM UMRS 791, University of Nantes, Laboratoire d'Ingénierie Ostéoarticulaire et Dentaire, LIOAD, School of Dental Surgery, 1 Place Alexis Ricordeau, Nantes Cedex 1, France.
Julien
Marion
M
Magne
David
D
Mallein-Gerin
Frédéric
F
Weiss
Pierre
P
Daculsi
Guy
G
Guicheux
Jérôme
J
D000818:Animals; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006132:Growth Plate / Q000098:blood supply / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D010012:Osteogenesis; D020033:Protein Isoforms / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor