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The bisphosphonate zoledronic acid regulates key angiogenesis-related genes in primary human gingival fibroblasts
- Source :
- Archives of Oral Biology. 63:7-14
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Background: Osteonecrosis of the jaws is recognised as a serious complication for patients receiving bisphosphonates. The anti-angiogenic effects of bisphosphonates have been implicated in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). The purpose of this study was to determine the effects of zoledronic acid on cultured human gingival fibroblasts in relation to the modulation of genes associated with angiogenic regulation.Methods: Primary cultures of fibroblasts were developed from gingival tissues excised during crown lengthening surgery from three patients. Cells were cultured with and without 30 mu M zoledronic acid for 6, 12 and 24h and cellular proliferation and migration investigated using CellTiter-Blue and scratch wound assays, respectively. Gene expression was determined using semi-quantitative PCR array technology that allowed the analysis of 84 pathway-focused genes known to be important in the regulation of angiogenesis.Results: Zoledronic acid increased the proliferation of the gingival fibroblasts in a dose dependent manner with 12 and 24 h of exposure. Scratch wounding of the human gingival fibroblasts and treatment with increasing doses and time exposure to zoledronic acid (ZA) inhibited their migration. Statistically significant increases in gene expression were found for RHOB, VEGFA, CD55 and BMP2 (p
- Subjects :
- Vascular Endothelial Growth Factor A
0301 basic medicine
Pathology
medicine.medical_specialty
Angiogenesis
RHOB
medicine.medical_treatment
Gingiva
Bone Morphogenetic Protein 2
Neovascularization, Physiologic
Polymerase Chain Reaction
Zoledronic Acid
03 medical and health sciences
0302 clinical medicine
Cell Movement
RhoB GTP-Binding Protein
Gene expression
medicine
Humans
rhoB GTP-Binding Protein
General Dentistry
Cells, Cultured
Chemokine CCL2
Cell Proliferation
Regulation of gene expression
Bone Density Conservation Agents
CD55 Antigens
Diphosphonates
Interleukin-6
business.industry
Imidazoles
Cell Biology
General Medicine
Fibroblasts
Bisphosphonate
Up-Regulation
Vascular endothelial growth factor A
030104 developmental biology
Zoledronic acid
Gene Expression Regulation
Otorhinolaryngology
030220 oncology & carcinogenesis
Cancer research
business
medicine.drug
Subjects
Details
- ISSN :
- 00039969
- Volume :
- 63
- Database :
- OpenAIRE
- Journal :
- Archives of Oral Biology
- Accession number :
- edsair.doi.dedup.....cd9d0ff878aabc477b4d0cb4277af033