Vascular endothelial growth factor stimulates chemotactic migration of primary human osteoblasts

Autor: Rolf E. Brenner, H Hausser, S. Kessler, Johannes Waltenberger, Christoph Dehio, Wolfhart Puhl, U Mayr-Wohlfart, K. P. Günther
Rok vydání: 2002
Předmět:
Vascular Endothelial Growth Factor A
medicine.medical_specialty
Histology
Physiology
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Basic fibroblast growth factor
Bone Morphogenetic Protein 2
Endothelial Growth Factors
Biology
Bone morphogenetic protein
Bone morphogenetic protein 2
chemistry.chemical_compound
Transforming Growth Factor beta
Internal medicine
medicine
Humans
Receptors
Growth Factor
Endochondral ossification
Cells
Cultured
Aged
Osteoblasts
Dose-Response Relationship
Drug
Chemotaxis
Growth factor
Receptor Protein-Tyrosine Kinases
Osteoblast
Middle Aged
Cell biology
Vascular endothelial growth factor
Vascular endothelial growth factor A
Receptors
Vascular Endothelial Growth Factor
medicine.anatomical_structure
Endocrinology
chemistry
Bone Morphogenetic Proteins
Fibroblast Growth Factor 2
Cell Division
Zdroj: Bone. 30:472-477
ISSN: 8756-3282
DOI: 10.1016/s8756-3282(01)00690-1
Popis: Recent studies have indicated a critical role for vascular endothelial growth factor (VEGF) during the process of endochondral ossification, in particular in coupling cartilage resorption with bone formation. Therefore, we studied the chemoattractive and proliferative properties of human VEGF-A on primary human osteoblasts (PHO) and compared these data with the effects of human basic fibroblast growth factor (bFGF) and human bone morphogenetic protein-2 (BMP-2). Furthermore, initial experiments were carried out to characterize VEGF-binding proteins on osteoblastic cells possibly involved in the response. For the first time, to our knowledge, we could demonstrate a chemoattractive effect of VEGF-A, but not VEGF-E, on primary human osteoblasts. The effect of VEGF-A was dose-dependent and did not reach a maximum within the concentration range tested (up to 10 ng/mL). The maximal effect observed was a chemotactic index (CI) of 2 at a concentration of 10 ng/mL. bFGF and BMP-2 exhibited maxima at 1.0 ng/mL with CI values of 2.5 and 2, respectively. In addition to its effect on cell migration, VEGF-A stimulated cell proliferation by up to 70%. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed the expression of VEGF receptors VEGFR-1 (Flt-1), VEGFR-2 (Kdr), and VEGFR-3 (Flt-4), as well as neuropilin-1 and -2. An in vitro kinase assay failed to demonstrate activation of VEGFR-2 upon stimulation with either VEGF-E or VEGF-A, consistent with the idea that the effect of VEGF-A on primary human osteoblasts is mediated via VEGFR-1. Taken together, our data establish that human osteoblasts respond to VEGF-A, suggesting a functional role for this growth factor in bone formation and remodeling.
Databáze: OpenAIRE
Externí odkaz: