Oleh Andrukhov1, Anja C Gemperli2, Yan Tang3, Nadia Howald2, Michel Dard4, Frank Falkensammer5, Andreas Moritz6, Xiaohui Rausch-Fan7. 1. Competence Centre of Periodontal Research, Bernhard Gottlieb School of Dentistry, Medical University of Vienna, Austria; Division of Conservative Dentistry, Periodontology and Prophylaxis, Bernhard Gottlieb School of Dentistry, Medical University of Vienna, Vienna, Austria. Electronic address: oleh.andrukhov@meduniwien.ac.at. 2. Institut Straumann AG, Basel, Switzerland. 3. Competence Centre of Periodontal Research, Bernhard Gottlieb School of Dentistry, Medical University of Vienna, Austria; Department of Stomatology, Xuanwu Hospital, Capital Medical University, Beijing, China. 4. Institut Straumann AG, Basel, Switzerland; New York University, College of Dentistry, Department of Periodontology and Implant Dentistry, New York, NY, USA. 5. Division of Orthodontics, Bernhard Gottlieb School of Dentistry, Medical University of Vienna, Vienna, Austria. 6. Division of Conservative Dentistry, Periodontology and Prophylaxis, Bernhard Gottlieb School of Dentistry, Medical University of Vienna, Vienna, Austria. 7. Competence Centre of Periodontal Research, Bernhard Gottlieb School of Dentistry, Medical University of Vienna, Austria; Division of Conservative Dentistry, Periodontology and Prophylaxis, Bernhard Gottlieb School of Dentistry, Medical University of Vienna, Vienna, Austria. Electronic address: xiaohui.rausch-fan@meduniwien.ac.at.
Abstract
OBJECTIVES: Enamel matrix derivative (EMD) is an effective biomaterial for periodontal tissue regeneration and might stimulate angiogenesis. In order to clarify mechanisms underlying its biological activity, we separated two EMD fractions with different molecular weight protein components and investigated their effects on human umbilical vein endothelial cells (HUVECs) in vitro. METHODS: Fraction Low-Molecular Weight (LMW) included proteins with a molecular weight (M.W.)<8kDa. Fraction LMW-depleted included proteins with M.W.>8kDa and lower than approximately 55kDa. The effect of EMD fractions on proliferation/viability, apoptosis, migration and expression of angiopoetin-2 (ang-2), von Willebrand factor (vWF), E-selectin, intracellular adhesion molecules 1 (ICAM-1), vascular endothelial growth factor (VEGF) receptors Flt-1 and KDR was investigated. RESULTS: The proliferation/viability of HUVECs was inhibited by both LMW and LMW-depleted at concentrations 100μg/ml, whereas EMD slightly increased cell proliferation/viability. The expression of all investigated proteins was up-regulated by EMD. However, differences in the effect of EMD fractions on the protein expression were observed. The effect of LMW-depleted on the expression of ICAM-1 and E-selectin was markedly higher compared to LMW. In contrast, the expression of vWF and VEGF receptors Flt-1 and KDR was primarily affected LMW than by LMW depleted. The expression of ang-2 was not influenced by LMW and LMW-depleted. HUVECs migration was stimulated more strongly by LMW than by EMD and LMW-depleted. CONCLUSION: Our in vitro study shows that the proteins composing EMD have different and specific biological activities and consequently have the ability to cover different aspects of EMD's biological and clinical effects.
OBJECTIVES: Enamel matrix derivative (EMD) is an effective biomaterial for periodontal tissue regeneration and might stimulate angiogenesis. In order to clarify mechanisms underlying its biological activity, we separated two EMD fractions with different molecular weight protein components and investigated their effects on human umbilical vein endothelial cells (HUVECs) in vitro. METHODS: Fraction Low-Molecular Weight (LMW) included proteins with a molecular weight (M.W.)<8kDa. Fraction LMW-depleted included proteins with M.W.>8kDa and lower than approximately 55kDa. The effect of EMD fractions on proliferation/viability, apoptosis, migration and expression of angiopoetin-2 (ang-2), von Willebrand factor (vWF), E-selectin, intracellular adhesion molecules 1 (ICAM-1), vascular endothelial growth factor (VEGF) receptors Flt-1 and KDR was investigated. RESULTS: The proliferation/viability of HUVECs was inhibited by both LMW and LMW-depleted at concentrations 100μg/ml, whereas EMD slightly increased cell proliferation/viability. The expression of all investigated proteins was up-regulated by EMD. However, differences in the effect of EMD fractions on the protein expression were observed. The effect of LMW-depleted on the expression of ICAM-1 and E-selectin was markedly higher compared to LMW. In contrast, the expression of vWF and VEGF receptors Flt-1 and KDR was primarily affected LMW than by LMW depleted. The expression of ang-2 was not influenced by LMW and LMW-depleted. HUVECs migration was stimulated more strongly by LMW than by EMD and LMW-depleted. CONCLUSION: Our in vitro study shows that the proteins composing EMD have different and specific biological activities and consequently have the ability to cover different aspects of EMD's biological and clinical effects.
Authors: Bin Guo; Chuhua Tang; Mingguo Wang; Zhongqi Zhao; Hassan A Shokoohi-Tabrizi; Bin Shi; Oleh Andrukhov; Xiaohui Rausch-Fan Journal: J Biomed Mater Res B Appl Biomater Date: 2020-02-25 Impact factor: 3.368