Controlling redox state by edaravone at transplantation site enhances bone regeneration.
Biomed Pharmacother
; 177: 117032, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38941894
ABSTRACT
In cell-based bone augmentation, transplanted cell dysfunction and apoptosis can occur due to oxidative stress caused by the overproduction of reactive oxygen species (ROS). Edaravone (EDA) is a potent free radical scavenger with potential medical applications. This study aimed to investigate the effect of controlling oxidative stress on bone regeneration using EDA. Bone marrow-derived cells were collected from 4-week-old rats, and EDA effects on cell viability and osteogenic differentiation were evaluated. Collagen gels containing PKH26-prelabeled cells were implanted into the calvarial defects of 12-week-old rats, followed by daily subcutaneous injections of normal saline or 500⯵M EDA for 4 d. Bone formation was examined using micro-computed tomography and histological staining. Immunofluorescence staining was performed for markers of oxidative stress, macrophages, osteogenesis, and angiogenesis. EDA suppressed ROS production and hydrogen peroxide-induced apoptosis, recovering cell viability and osteoblast differentiation. EDA treatment in vivo increased new bone formation. EDA induced the transition of the macrophage population toward the M2 phenotype. The EDA group also exhibited stronger immunofluorescence for vascular endothelial growth factor and CD31. In addition, more PKH26-positive and PKH26-osteocalcin-double-positive cells were observed in the EDA group, indicating that transplanted cell survival was prolonged, and they differentiated into bone-forming cells. This could be attributed to oxidative stress suppression at the transplantation site by EDA. Collectively, local administration using EDA facilitates bone regeneration by improving the local environment and angiogenesis, prolonging survival, and enhancing the osteogenic capabilities of transplanted cells.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteogenesis
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Oxidation-Reduction
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Bone Regeneration
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Cell Differentiation
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Cell Survival
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Reactive Oxygen Species
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Rats, Sprague-Dawley
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Oxidative Stress
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Edaravone
Limits:
Animals
Language:
En
Journal:
Biomed Pharmacother
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: