Recombinant bone morphogenetic protein-2 induces up-regulation of vascular endothelial growth factor and interleukin 6 in human pre-osteoblasts: Role of reactive oxygen species

Sara Akeel, Ahmed El-Awady, Khaled Hussein, Mona El-Refaey, Mohammed Elsayed Elsalanty, Mohamed M.H. Sharawy, Mohamed Al-Shabrawey

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Objective: Bone morphogenetic proteins (BMPs) and vascular endothelial growth factor (VEGF) have been reported in many studies to play a major role in the communication between endothelial cells and osteoblasts. The inflammatory reaction and relative hypoxia at the site of bone injury are the first stages of the fracture repair. rhBMP-2 has been used extensively in spinal fusion and reconstruction of maxillofacial bone defects with main complication is the formation of seroma. The aim of this study was to test whether rhBMP-2 regulates the expression of the angiogenic and inflammatory mediators in pre-osteoblasts via generating reactive oxygen species (ROS). Methods: rhBMP-2 effect on angiogenesis and inflammatory genes was assessed using normal human osteoblasts (NHOst). Angiogenesis genes were measured using angiogenic PCR array. VEGF and IL6 production were analysed using ELISA kit and real-time PCR. ROS production was assessed using dihydroethidine and dichlorofluorescein staining and lipid peroxidation. HIF-1α immunoreactivity was performed using immunofluorescence staining. Results: There was an increase in the pro-angiogenic and -inflammatory genes as well as VEGF and IL6 protein expression in NHOst by rhBMP-2. This increase in VEGF and IL6 was blocked by the ROS scavenger N-acetyl cysteine (NAC). Conclusion: The regulatory effect of rhBMP-2 on angiogenesis and inflammation is mediated through a ROS-dependent mechanism, which involves upregulation of crucial angiogenic and inflammatory mediators such as VEGF and IL6. These findings highlight the need for future studies to identify new therapeutic targets downstream from rhBMP-2 to potentiate its beneficial effect or limit its complications such as seroma formation.

Original languageEnglish (US)
Pages (from-to)445-452
Number of pages8
JournalArchives of Oral Biology
Volume57
Issue number5
DOIs
StatePublished - May 1 2012

Fingerprint

Bone Morphogenetic Protein 2
Osteoblasts
Recombinant Proteins
Vascular Endothelial Growth Factor A
Interleukin-6
Reactive Oxygen Species
Up-Regulation
Seroma
Staining and Labeling
Genes
Bone and Bones
Spinal Fusion
Bone Morphogenetic Proteins
Lipid Peroxidation
Fluorescent Antibody Technique
Cysteine
Real-Time Polymerase Chain Reaction
Endothelial Cells
Enzyme-Linked Immunosorbent Assay
Communication

Keywords

  • IL6
  • Osteoblasts
  • VEGF
  • rhBMP-2

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Dentistry(all)
  • Cell Biology

Cite this

@article{b0281669d5664838804a5b706cdaea2b,
title = "Recombinant bone morphogenetic protein-2 induces up-regulation of vascular endothelial growth factor and interleukin 6 in human pre-osteoblasts: Role of reactive oxygen species",
abstract = "Objective: Bone morphogenetic proteins (BMPs) and vascular endothelial growth factor (VEGF) have been reported in many studies to play a major role in the communication between endothelial cells and osteoblasts. The inflammatory reaction and relative hypoxia at the site of bone injury are the first stages of the fracture repair. rhBMP-2 has been used extensively in spinal fusion and reconstruction of maxillofacial bone defects with main complication is the formation of seroma. The aim of this study was to test whether rhBMP-2 regulates the expression of the angiogenic and inflammatory mediators in pre-osteoblasts via generating reactive oxygen species (ROS). Methods: rhBMP-2 effect on angiogenesis and inflammatory genes was assessed using normal human osteoblasts (NHOst). Angiogenesis genes were measured using angiogenic PCR array. VEGF and IL6 production were analysed using ELISA kit and real-time PCR. ROS production was assessed using dihydroethidine and dichlorofluorescein staining and lipid peroxidation. HIF-1α immunoreactivity was performed using immunofluorescence staining. Results: There was an increase in the pro-angiogenic and -inflammatory genes as well as VEGF and IL6 protein expression in NHOst by rhBMP-2. This increase in VEGF and IL6 was blocked by the ROS scavenger N-acetyl cysteine (NAC). Conclusion: The regulatory effect of rhBMP-2 on angiogenesis and inflammation is mediated through a ROS-dependent mechanism, which involves upregulation of crucial angiogenic and inflammatory mediators such as VEGF and IL6. These findings highlight the need for future studies to identify new therapeutic targets downstream from rhBMP-2 to potentiate its beneficial effect or limit its complications such as seroma formation.",
keywords = "IL6, Osteoblasts, VEGF, rhBMP-2",
author = "Sara Akeel and Ahmed El-Awady and Khaled Hussein and Mona El-Refaey and Elsalanty, {Mohammed Elsayed} and Sharawy, {Mohamed M.H.} and Mohamed Al-Shabrawey",
year = "2012",
month = "5",
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doi = "10.1016/j.archoralbio.2011.10.002",
language = "English (US)",
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TY - JOUR

T1 - Recombinant bone morphogenetic protein-2 induces up-regulation of vascular endothelial growth factor and interleukin 6 in human pre-osteoblasts

T2 - Role of reactive oxygen species

AU - Akeel, Sara

AU - El-Awady, Ahmed

AU - Hussein, Khaled

AU - El-Refaey, Mona

AU - Elsalanty, Mohammed Elsayed

AU - Sharawy, Mohamed M.H.

AU - Al-Shabrawey, Mohamed

PY - 2012/5/1

Y1 - 2012/5/1

N2 - Objective: Bone morphogenetic proteins (BMPs) and vascular endothelial growth factor (VEGF) have been reported in many studies to play a major role in the communication between endothelial cells and osteoblasts. The inflammatory reaction and relative hypoxia at the site of bone injury are the first stages of the fracture repair. rhBMP-2 has been used extensively in spinal fusion and reconstruction of maxillofacial bone defects with main complication is the formation of seroma. The aim of this study was to test whether rhBMP-2 regulates the expression of the angiogenic and inflammatory mediators in pre-osteoblasts via generating reactive oxygen species (ROS). Methods: rhBMP-2 effect on angiogenesis and inflammatory genes was assessed using normal human osteoblasts (NHOst). Angiogenesis genes were measured using angiogenic PCR array. VEGF and IL6 production were analysed using ELISA kit and real-time PCR. ROS production was assessed using dihydroethidine and dichlorofluorescein staining and lipid peroxidation. HIF-1α immunoreactivity was performed using immunofluorescence staining. Results: There was an increase in the pro-angiogenic and -inflammatory genes as well as VEGF and IL6 protein expression in NHOst by rhBMP-2. This increase in VEGF and IL6 was blocked by the ROS scavenger N-acetyl cysteine (NAC). Conclusion: The regulatory effect of rhBMP-2 on angiogenesis and inflammation is mediated through a ROS-dependent mechanism, which involves upregulation of crucial angiogenic and inflammatory mediators such as VEGF and IL6. These findings highlight the need for future studies to identify new therapeutic targets downstream from rhBMP-2 to potentiate its beneficial effect or limit its complications such as seroma formation.

AB - Objective: Bone morphogenetic proteins (BMPs) and vascular endothelial growth factor (VEGF) have been reported in many studies to play a major role in the communication between endothelial cells and osteoblasts. The inflammatory reaction and relative hypoxia at the site of bone injury are the first stages of the fracture repair. rhBMP-2 has been used extensively in spinal fusion and reconstruction of maxillofacial bone defects with main complication is the formation of seroma. The aim of this study was to test whether rhBMP-2 regulates the expression of the angiogenic and inflammatory mediators in pre-osteoblasts via generating reactive oxygen species (ROS). Methods: rhBMP-2 effect on angiogenesis and inflammatory genes was assessed using normal human osteoblasts (NHOst). Angiogenesis genes were measured using angiogenic PCR array. VEGF and IL6 production were analysed using ELISA kit and real-time PCR. ROS production was assessed using dihydroethidine and dichlorofluorescein staining and lipid peroxidation. HIF-1α immunoreactivity was performed using immunofluorescence staining. Results: There was an increase in the pro-angiogenic and -inflammatory genes as well as VEGF and IL6 protein expression in NHOst by rhBMP-2. This increase in VEGF and IL6 was blocked by the ROS scavenger N-acetyl cysteine (NAC). Conclusion: The regulatory effect of rhBMP-2 on angiogenesis and inflammation is mediated through a ROS-dependent mechanism, which involves upregulation of crucial angiogenic and inflammatory mediators such as VEGF and IL6. These findings highlight the need for future studies to identify new therapeutic targets downstream from rhBMP-2 to potentiate its beneficial effect or limit its complications such as seroma formation.

KW - IL6

KW - Osteoblasts

KW - VEGF

KW - rhBMP-2

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