Expression and localization of VEGF receptors in human fetal skeletal tissues

Mirca Marini, Erica Sarchielli¹, Mariateresa Toce¹, Alessandro Acocella², Roberto Bertolai², Carlotta Ciulli³, Claudio Orlando³, Eleonora Sgambati⁴ and Gabriella Barbara Vannelli<sup>1

1</sup>Department of Anatomy Histology and Forensic Medicine, University of Florence, Florence, Italy, ²Department of Maxillo-Facial Surgery, University of Florence, Florence, Italy, ³Clinical Biochemistry Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy and ⁴Department of Sciences and Technologies for Environment, University of Molise, Pesche, Italy.

Offprint requests to: Mirca Marini, Department of Anatomy Histology and Forensic Medicine, University of Florence, Viale Morgagni 85, 50134 Florence, Italy. e-mail: mirca.marini@unifi.it


Summary. During development the vertebrate skeleton is the product of deriving cells from distinct embryonic lineages. The craniofacial skeleton is formed by migrating cranial neural crest cells, whereas the axial and limb skeletons are derived from mesodermal cells.
The Vascular Endothelial Growth Factors (VEGFs) / receptors (VEGFRs) system plays an important role in angiogenesis, as well as osteogenesis, during bone development, growth, and remodeling, attracting endothelial cells and osteoclasts and stimulating osteoblast differentiation. Recent evidence has shown that during development VEGFR-3 is also expressed in neural and glial precursors of forebrain and cerebellum, as well as in the eye.
In this study, we found that VEGFR-1, VEGFR-2 and VEGFR-3 are expressed in human bone both in fetal and adult life. The gene expression levels were significantly higher in fetal samples especially in mandibles. In addition, higher levels of VEGFR-3 in orofacial district were confirmed by western blotting analysis. We also observed that in fetal mandibular samples VEGFRs colocalized in several osteoblasts, osteoclasts and osteoprogenitor cells. Furthermore, some cells coexpressed VEGFR-3 and ET-1, a marker of neural crest cells. The results demonstrated different expression of VEGFRs in human mandibular and femoral bones which could be correlated to their different structure, function and development during organogenesis. VEGFR-3 might represent a specific signal for ectomesenchymal lineage differentiation during early human development. Histol Histopathol 27, 1579-1587 (2012)