Abstract
It is well known that angiogenesis is essential for the replacement of cartilage by bone during skeletal growth and regeneration. To address angiogenesis of endochondral ossification in the condyle, we examined the appearance of vascular endothelial growth factor (VEGF) and its receptor Flt-1 in condylar cartilage of the growing rat. The early expression of VEGF at various sites during condylar cartilage development indicates that VEGF plays a role in the regulation of angiogenesis at each site of bone formation. From the findings of Flt-1 immunoreactivity, the VEGF produced by the chondrocytes of the hypertrophic zone should contribute to the promotion of endothelial cell proliferation and to stimulate migration and activation of osteoclasts in condylar cartilage, resulting in the invasion of these cells into the mineralized zone.
Similar content being viewed by others
References
Baleon B, Sozzani S, Zhou D, Weich HA, Mantovani A, Marme D (1996) Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. Blood 87:3336–3343
Carlevaro MF, Cermelli S, Cancedda R, Cancedda DF (2000) Vascular endothelial growth factor (VEGF) in cartilage neovascularization and chondrocyte differentiation: auto-paracrine role during endochondral bone formation. J Cell Sci 113:59–69
Christofori G, Naik P, Hanahan D (1995) Vascular endothelial growth factor and its receptors, flt-1, are expressed in normal pancreatic islets and throughout islet cell tumorigenesis. Mol Endocrinol 9:1760–1770
Claffey KP, Wilkison WO, Spiegelman BM (1992) Vascular endothelial growth factor. Regulation by cell differentiation and activated second messenger pathways. J Biol Chem 267:16317–16322
Conn G, Bayne ML, Soderman DD, Kwok PW, Sullivan KA, Palisi TM, Hope DA, Thomas KA (1990) Amino acid and cDNA sequences of a vascular endothelial cell mitogen that is homologous to platelet-derived growth factor. Proc Natl Acad Sci U S A 87:2628–2632
Connolly DT (1991) Vascular permeability factor: a unique regulator of blood vessel function. J Cell Biochem 47:219–223
Copray JC, Jansen HW, Duterloo HS (1986) Growth and growth pressure of mandibular condylar and some primary cartilages of the rat in vitro. Am J Orthod Dentofacial Orthop 90:19–28
Dibbets JM, Carlson D (1995) Implications of temporomandibular disorders for facial growth and orthodontic treatment. Semin Orthod 1:258–272
Ferrara N, Davis-Smyth T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18:4–25
Garcia-Ramirez M, Toran N, Andaluz P, Carrascosa A, Audi L (2000) Vascular endothelial growth factor is expressed in human fetal growth cartilage. J Bone Miner Res 15:534–540
Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N (1999) VEGF couples hypertrophic cartilage remodelling, ossification and angiogenesis during endochondral ossification. Nat Med 5:623–628
Harada S, Nagy JA, Sullivan KA, Thomas KA, Endo N, Rodan GA, Rodan SB (1994) Induction of vascular endothelial growth factor expression by prostaglandin E2 and E1 in osteoblasts. J Clin Invest 93:2490–2496
Harper J, Klagsbrun M (1999) Cartilage to bone: angiogenesis leads the way. Nat Med 5:617–618
Horner A, Bishop NJ, Bord S, Beeton C, Kelsall AW, Coleman N, Compston JE (1999) Immunolocalisation of vascular endothelial growth factor (VEGF) in human neonatal growth plate cartilage. J Anat 194:519–524
Horner A, Bord S, Kelsall AW, Coleman N, Compston JE (2001) Tie2 ligands angiopoietin-1 and angiopoietin-2 are coexpressed with vascular endothelial cell growth factor in growing human bone. Bone 28:65–71
Ichigatani M, Saga T, Yamaki K, Yoshizuka M (2001) Appearance of vascular endothelial growth factor (VEGF) in femoral head in the growing rat. Histol Histopathol 16:463–468
Kearney JB, Kappas NC, Ellerstrom C, DiPaola FW, Bautch VL(2004) The VEGF receptor flt-1 (VEGFR-1) is a positive modulator of vascular sprout formation and branching morphogenesis. Blood. [Epub ahead of print]
Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309
Nakagawa M, Kaneda T, Arakawa T, Morita S, Sato T, Yamada T, Hanada K, Kumegawa M, Hakeda Y (2000) Vascular endothelial growth factor (VEGF) directly enhances osteoclastic bone resorption and survival of mature osteoclasts. FEBS Lett 473:161–164
Niida S, Kaku M, Amano H, Yoshida H, Kataoka H, Nishikawa S, Tanne K, Maeda N, Nishikawa S, Kodama H (1999) Vascular endothelial growth factor can substitute for macrophage colony-stimulating factor in the support of osteoclastic bone resorption. J Exp Med 190:293–298
Pepper MS, Ferrara N, Orci L, Montesano R (1991) Vascular endothelial growth factor (VEGF) induces plasminogen activators and plasminogen activator inhibitor-1 in microvascular endothelial cells. Biochem Biophys Res Commun 181:902–906
Phillips HS, Hains J, Leung DW, Ferrara N (1990) Vascular endothelial growth factor is expressed in rat corpus luteum. Endocrinology 127:965–967
Pufe T, Petersen W, Tillmann B, Mentlein R (2001a) The splice variants VEGF121 and VEGF189 of the angiogenic peptide vascular endothelial growth factor are expressed in osteoarthritic cartilage. Arthritis Rheum 44:1082–1088
Pufe T, Petersen W, Tillmann B, Mentlein R (2001b) Splice variants VEGF121 and VEGF165 of the angiogenic peptide vascular endothelial cell growth factor are expressed in the synovial tissue of patients with rheumatoid arthritis. J Rheumatol 28:1482–1485
Simon M, Grone HJ, Johren O, Kullmer J, Plate KH, Risau W, Fuchs E (1995) Expression of vascular endothelial growth factor and its receptors in human renal ontogenesis and in adult kidney. Am J Physiol 268:F240–F250
Takano-Yamamoto T, Soma S, Nakagawa K, Kobayashi Y, Kawakami M, Sakuda M (1991) Comparison of the effects of hydrostatic compressive force on glycosaminoglycan synthesis and proliferation in rabbit chondrocytes from mandibular condylar cartilage, nasal septum, and spheno-occipital synchondrosis in vitro. Am J Orthod Dentofacial Orthop 99:448–455
Acknowledgements
This research was supported by a grant (number 14571950) for Science Research from the Ministry of Education, Science and Culture, Japan.
Author information
Authors and Affiliations
Corresponding author
Additional information
Junko Aoyama and Eiji Tanaka contributed equally to this work
Rights and permissions
About this article
Cite this article
Aoyama, J., Tanaka, E., Miyauchi, M. et al. Immunolocalization of vascular endothelial growth factor in rat condylar cartilage during postnatal development. Histochem Cell Biol 122, 35–40 (2004). https://doi.org/10.1007/s00418-004-0671-3
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00418-004-0671-3