Expression of vascular endothelial growth factor receptors coincide with blood vessel in-growth and reactive bone remodelling in experimental intervertebral disc degeneration.
OBJECTIVE
To analyze immunohistochemically the localization of the VEGF receptors in experimental intervertebral disc degeneration tissues in a pig model.


METHODS
In six domestic pigs, the cranial bony endplate of the L4 vertebra were perforated into the nucleus pulposus. Three months postoperatively, the animals were sacrificed and the experimental and control vertebrae, complete with intervertebral discs, were excised and subjected for immunohistochemical staining of vascular endothelial growth factor receptors (VEGFR) along with VEGF - A, -C, -D and blood and lymphatic vessel markers vWF and LYVE-1.


RESULTS
The results of immunohistochemical analysis of experimental samples showed VEGFR-1 (Flt-1) expression in intervertebral disc and all paradiscal tissues studied. In control samples expression of VEGFR-1 was lower and absent in the intervertebral discs. Comparatively less of VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4) than VEGFR-1was found in degenerated intervertebral discs and paradiscal tissues. In contiguous control intervertebral discs and control paradiscal tissues VEGFR-2 and-3 receptors were expressed to a lower extent than in experimental tissues or were even totally absent. Also growth factors VEGF-A, -C, -D, as well as von Willebrand factor and to a much lower extent LYVE-1 were differently expressed in experimental and control intervertebral discs.


CONCLUSIONS
In experimental intervertebral disc degeneration, VEGF receptors were expressed in the damaged disc and paradiscal tissues. In the same tissues, VEGF-A, -C, and -D, signs of blood and lymphatic vessel in-growth and reactive/adaptive vertebral bone remodelling were found.
Salo
J
J
Department of Orthopaedic Surgery, Helsinki University Central Hospital, Helsinki, Finland.
Kaigle Holm
A
A
Indahl
A
A
Mackiewicz
Z
Z
Sukura
A
A
Holm
S
S
Jämsen
E
E
Konttinen
Y T
YT
D000818:Animals; D000906:Antibodies; D001808:Blood Vessels / Q000378:metabolism; D016723:Bone Remodeling / Q000502:physiology*; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000098:blood supply / Q000473:pathology; D007405:Intervertebral Disc Displacement / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D008159:Lumbar Vertebrae / Q000098:blood supply / Q000473:pathology; D042601:Lymphatic Vessels / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000276:immunology / Q000378:metabolism*; D034421:Sus scrofa; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000276:immunology / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000276:immunology / Q000378:metabolism; D014841:von Willebrand Factor / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D014841:von Willebrand Factor; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3