Immunolocalisation of Vascular Endothelial Growth Factor (VEGF) in Human Neonatal Growth Plate Cartilage

Overview

Journal J Anat

Specialty Anatomy & Histology

Date 1999 Aug 13

PMID 10445820

Citations 24

Authors

A Horner

N J Bishop

S Bord

C Beeton

A W Kelsall

N Coleman

J E Compston

Affiliations

Soon will be listed here.

Abstract

Angiogenesis is essential for the replacement of cartilage by bone during growth and repair. In order to obtain a better understanding of the mechanisms regulating vascular invasion at sites of endochondral ossification we have investigated the expression of the endothelial cell-specific mitogen, vascular endothelial growth factor (VEGF), by chondrocytes in human neonatal growth plates. VEGF was absent from chondrocytes in the resting zone and only weakly expressed by occasional chondrocytes in the proliferating region. In the hypertrophic zone the number of chondrocytes stained and the intensity of staining for VEGF increased with chondrocyte hypertrophy, maximum expression of VEGF being observed in chondrocytes in the lower hypertrophic and mineralised regions of the cartilage. These observations provide the first demonstration of the presence of VEGF in situ in developing human bone and are consistent with in vitro observations demonstrating the upregulation of proangiogenic growth factor production with increasing chondrocyte hypertrophy. The presence of numerous small blood vessels and vascular structures in the subchondral region where VEGF expression was maximal indicates that VEGF produced by hypertrophic chondrocytes may play a key role in the regulation of vascular invasion of the growth plate.

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References

Ohba Y, Goto Y, Kimura Y, Suzuki F, Hisa T, Takahashi K . Purification of an angiogenesis inhibitor from culture medium conditioned by a human chondrosarcoma-derived chondrocytic cell line, HCS-2/8. Biochim Biophys Acta. 1995; 1245(1):1-8. DOI: 10.1016/0304-4165(95)00065-j. View

Descalzi Cancedda F, Melchiori A, Benelli R, Gentili C, Masiello L, Campanile G . Production of angiogenesis inhibitors and stimulators is modulated by cultured growth plate chondrocytes during in vitro differentiation: dependence on extracellular matrix assembly. Eur J Cell Biol. 1995; 66(1):60-8. View

Alini M, Marriott A, Chen T, Abe S, Poole A . A novel angiogenic molecule produced at the time of chondrocyte hypertrophy during endochondral bone formation. Dev Biol. 1996; 176(1):124-32. DOI: 10.1006/dbio.1996.9989. View

Horner A, Bord S, Kemp P, Grainger D, Compston J . Distribution of platelet-derived growth factor (PDGF) A chain mRNA, protein, and PDGF-alpha receptor in rapidly forming human bone. Bone. 1996; 19(4):353-62. DOI: 10.1016/s8756-3282(96)00217-7. View

Grimmond S, Lagercrantz J, Drinkwater C, Silins G, Townson S, Pollock P . Cloning and characterization of a novel human gene related to vascular endothelial growth factor. Genome Res. 1996; 6(2):124-31. DOI: 10.1101/gr.6.2.124. View

Carlevaro M, Albini A, Ribatti D, Gentili C, Benelli R, Cermelli S . Transferrin promotes endothelial cell migration and invasion: implication in cartilage neovascularization. J Cell Biol. 1997; 136(6):1375-84. PMC: 2132523. DOI: 10.1083/jcb.136.6.1375. View

Nauck M, Roth M, Tamm M, Eickelberg O, Wieland H, Stulz P . Induction of vascular endothelial growth factor by platelet-activating factor and platelet-derived growth factor is downregulated by corticosteroids. Am J Respir Cell Mol Biol. 1997; 16(4):398-406. DOI: 10.1165/ajrcmb.16.4.9115750. View

Enholm B, Paavonen K, Ristimaki A, Kumar V, Gunji Y, Klefstrom J . Comparison of VEGF, VEGF-B, VEGF-C and Ang-1 mRNA regulation by serum, growth factors, oncoproteins and hypoxia. Oncogene. 1997; 14(20):2475-83. DOI: 10.1038/sj.onc.1201090. View

Hu J, Hastings G, Cherry S, Gentz R, Ruben S, Coleman T . A novel regulatory function of proteolytically cleaved VEGF-2 for vascular endothelial and smooth muscle cells. FASEB J. 1997; 11(6):498-504. DOI: 10.1096/fasebj.11.6.9194531. View

10.

Yamada Y, Nezu J, SHIMANE M, Hirata Y . Molecular cloning of a novel vascular endothelial growth factor, VEGF-D. Genomics. 1997; 42(3):483-8. DOI: 10.1006/geno.1997.4774. View

11.

Fitz L, Morris J, Towler P, Long A, Burgess P, Greco R . Characterization of murine Flt4 ligand/VEGF-C. Oncogene. 1997; 15(5):613-8. DOI: 10.1038/sj.onc.1201191. View

12.

Mori S, Yoshikawa H, Hashimoto J, Ueda T, Funai H, Kato M . Antiangiogenic agent (TNP-470) inhibition of ectopic bone formation induced by bone morphogenetic protein-2. Bone. 1998; 22(2):99-105. DOI: 10.1016/s8756-3282(97)00248-2. View

13.

Horner A, Kemp P, Summers C, Bord S, Bishop N, Kelsall A . Expression and distribution of transforming growth factor-beta isoforms and their signaling receptors in growing human bone. Bone. 1998; 23(2):95-102. DOI: 10.1016/s8756-3282(98)00080-5. View

14.

Holder N . The onset of osteogenesis in the developing chick limb. J Embryol Exp Morphol. 1978; 44:15-29. View

15.

Senger D, Perruzzi C, Feder J, Dvorak H . A highly conserved vascular permeability factor secreted by a variety of human and rodent tumor cell lines. Cancer Res. 1986; 46(11):5629-32. View

16.

GOSPODAROWICZ D, Abraham J, Schilling J . Isolation and characterization of a vascular endothelial cell mitogen produced by pituitary-derived folliculo stellate cells. Proc Natl Acad Sci U S A. 1989; 86(19):7311-5. PMC: 298051. DOI: 10.1073/pnas.86.19.7311. View

17.

Leung D, Cachianes G, Kuang W, Goeddel D, Ferrara N . Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989; 246(4935):1306-9. DOI: 10.1126/science.2479986. View

18.

Conn G, SODERMAN D, Schaeffer M, Wile M, Hatcher V, Thomas K . Purification of a glycoprotein vascular endothelial cell mitogen from a rat glioma-derived cell line. Proc Natl Acad Sci U S A. 1990; 87(4):1323-7. PMC: 53467. DOI: 10.1073/pnas.87.4.1323. View

19.

Fina L, Molgaard H, Robertson D, BRADLEY N, Monaghan P, Delia D . Expression of the CD34 gene in vascular endothelial cells. Blood. 1990; 75(12):2417-26. View

20.

Moses M, Sudhalter J, Langer R . Identification of an inhibitor of neovascularization from cartilage. Science. 1990; 248(4961):1408-10. DOI: 10.1126/science.1694043. View