Sildenafil, a phosphodiesterase-5 inhibitor, stimulates angiogenesis and bone regeneration in an atrophic non-union model in mice.
Angiogenesis
Bone regeneration
Fracture healing
Mice
Non-union
Segmental defect
Sildenafil
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
08 09 2023
08 09 2023
Historique:
received:
10
06
2023
accepted:
14
08
2023
medline:
11
9
2023
pubmed:
9
9
2023
entrez:
8
9
2023
Statut:
epublish
Résumé
Non-union formation represents a major complication in trauma and orthopedic surgery. The phosphodiesterase-5 (PDE-5) inhibitor sildenafil has been shown to exert pro-angiogenic and pro-osteogenic effects in vitro and in vivo. Therefore, the aim of the present study was to analyze the impact of sildenafil in an atrophic non-union model in mice. After creation of a 1.8 mm segmental defect, mice femora were stabilized by pin-clip fixation. Bone regeneration was analyzed by means of X-ray, biomechanics, photoacoustic and micro-computed tomography (µCT) imaging as well as histological, immunohistochemical and Western blot analyses at 2, 5 and 10 weeks after surgery. The animals were treated daily with either 5 mg/kg body weight sildenafil (n = 35) or saline (control; n = 35) per os. Bone formation was markedly improved in defects of sildenafil-treated mice when compared to controls. This was associated with a higher bending stiffness as well as an increased number of CD31-positive microvessels and a higher oxygen saturation within the callus tissue. Moreover, the bone defects of sildenafil-treated animals contained more tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD68-positive macrophages and exhibited a higher expression of the pro-angiogenic and pro-osteogenic markers cysteine rich protein (CYR)61 and vascular endothelial growth factor (VEGF) when compared to controls. These findings demonstrate that sildenafil acts as a potent stimulator of angiogenesis and bone regeneration in atrophic non-unions.
Identifiants
pubmed: 37684656
doi: 10.1186/s12967-023-04441-8
pii: 10.1186/s12967-023-04441-8
pmc: PMC10486066
doi:
Substances chimiques
Sildenafil Citrate
BW9B0ZE037
Phosphodiesterase 5 Inhibitors
0
Cyclic Nucleotide Phosphodiesterases, Type 5
EC 3.1.4.35
Vascular Endothelial Growth Factor A
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
607Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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