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Rebamipide delivered by brushite cement enhances osteoblast and macrophage proliferation.
- Source :
-
PloS one [PLoS One] 2015 May 29; Vol. 10 (5), pp. e0128324. Date of Electronic Publication: 2015 May 29 (Print Publication: 2015). - Publication Year :
- 2015
-
Abstract
- Many of the bioactive agents capable of stimulating osseous regeneration, such as bone morphogenetic protein-2 (BMP-2) or prostaglandin E2 (PGE2), are limited by rapid degradation, a short bioactive half-life at the target site in vivo, or are prohibitively expensive to obtain in large quantities. Rebamipide, an amino acid modified hydroxylquinoline, can alter the expression of key mediators of bone anabolism, cyclo-oxygenase 2 (COX-2), BMP-2 and vascular endothelial growth factor (VEGF), in diverse cell types such as mucosal and endothelial cells or chondrocytes. The present study investigates whether Rebamipide enhances proliferation and differentiation of osteoblasts when delivered from brushite cement. The reactive oxygen species (ROS) quenching ability of Rebampide was tested in macrophages as a measure of bioactivity following drug release incubation times, up to 14 days. Rebamipide release from brushite occurs via non-fickian diffusion, with a rapid linear release of 9.70% ± 0.37% of drug per day for the first 5 days, and an average of 0.5%-1% per day thereafter for 30 days. Rebamipide slows the initial and final cement setting time by up to 3 and 1 minute, respectively, but does not significantly reduce the mechanical strength below 4% (weight percentage). Pre-osteoblast proliferation increases by 24% upon exposure to 0.4 uM Rebamipide, and by up to 73% when Rebamipide is delivered via brushite cement. Low doses of Rebamipide do not adversely affect peak alkaline phosphatase activity in differentiating pre-osteoblasts. Rebamipide weakly stimulates proliferation in macrophages at low concentrations (118 ± 7.4% at 1 uM), and quenches ROS by 40-60%. This is the first investigation of Rebamipide in osteoblasts.
- Subjects :
- Alanine pharmacokinetics
Alanine pharmacology
Animals
Bone Cements pharmacokinetics
Calcium Phosphates pharmacokinetics
Cell Differentiation drug effects
Cell Line
Delayed-Action Preparations pharmacokinetics
Delayed-Action Preparations pharmacology
Macrophages cytology
Mice
Osteoblasts cytology
Quinolones pharmacokinetics
Alanine analogs & derivatives
Bone Cements pharmacology
Calcium Phosphates pharmacology
Cell Proliferation drug effects
Macrophages metabolism
Osteoblasts metabolism
Quinolones pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 10
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 26023912
- Full Text :
- https://doi.org/10.1371/journal.pone.0128324