The modulation of gene expression in osteoblasts by thrombin coated on biphasic calcium phosphate ceramic

For many years, fibrin sealants were associated with bone substitutes to promote bone healing. However, the osteoblastic response to fibrin sealant components remains poorly documented. In this study, MC3T3-E1 osteoblastic cells were cultured on biphasic calcium phosphate ceramic (MBCP ®) coated wit...

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Veröffentlicht in:Biomaterials 2006-05, Vol.27 (15), p.2934-2943
Hauptverfasser: Bluteau, Gilles, Pilet, Paul, Bourges, Xavier, Bilban, Melitta, Spaethe, Reiner, Daculsi, Guy, Guicheux, Jérôme
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container_end_page 2943
container_issue 15
container_start_page 2934
container_title Biomaterials
container_volume 27
creator Bluteau, Gilles
Pilet, Paul
Bourges, Xavier
Bilban, Melitta
Spaethe, Reiner
Daculsi, Guy
Guicheux, Jérôme
description For many years, fibrin sealants were associated with bone substitutes to promote bone healing. However, the osteoblastic response to fibrin sealant components remains poorly documented. In this study, MC3T3-E1 osteoblastic cells were cultured on biphasic calcium phosphate ceramic (MBCP ®) coated with Tissucol ® components (thrombin and fibrinogen). Analysis of osteoblastic differentiation markers by RT-PCR revealed that MBCP ® coated with Tissucol ® stimulated mRNA levels for osteocalcin and alkaline phosphatase (ALP). Of all the components of Tissucol ®, thrombin has been reported to affect osteoblastic behavior. Our results demonstrated that low thrombin concentrations (0.5–5 U/ml) stimulated mRNA levels for ALP, whereas high thrombin concentrations (50–100 U/ml) decreased mRNA levels for ALP and PTH/PTHrP receptor and also increased mRNA level for the osteoclastogenesis inhibitor OPG. As thrombin stimulated angiogenesis, we then wondered whether thrombin could influence the expression of angiogenic factors. Low thrombin concentrations were shown to up-regulate mRNA levels for VEGF-B and VEGF-R1, suggesting an autocrine/paracrine role for VEGF-B. Higher thrombin concentrations also up-regulated mRNA for VEGF-A and neuropilin-1. In conclusion, the association of MBCP ® with thrombin and fibrinogen appears to be a convenient scaffold for bone cell differentiation. Thrombin could also acts at the cellular level by increasing the angiogenic potential of osteoblasts as well as their responsiveness to thrombin and VEGF.
doi_str_mv 10.1016/j.biomaterials.2006.01.004
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subjects Animals
Biphasic calcium phosphate
Bone Substitutes - administration & dosage
Bone Substitutes - pharmacology
Calcium Phosphates - chemistry
Cell Differentiation - drug effects
Cell Proliferation - drug effects
Cell Size - drug effects
Ceramics - chemistry
Coated Materials, Biocompatible - administration & dosage
Differentiation
Fibrin glue
Fibrin Tissue Adhesive - administration & dosage
Fibrin Tissue Adhesive - chemistry
Gene Expression Regulation - drug effects
Gene Expression Regulation - physiology
Mice
NIH 3T3 Cells
Osteoblast
Osteoblasts - cytology
Osteoblasts - drug effects
Osteoblasts - physiology
Receptors, Thrombin - metabolism
Thrombin
Thrombin - administration & dosage
Thrombin - chemistry
Vascular Endothelial Growth Factor A - metabolism
VEGF
title The modulation of gene expression in osteoblasts by thrombin coated on biphasic calcium phosphate ceramic
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