Please use this identifier to cite or link to this item: doi:10.22028/D291-41506
Title: Cilostazol Stimulates Angiogenesis and Accelerates Fracture Healing in Aged Male and Female Mice by Increasing the Expression of PI3K and RUNX2
Author(s): Menger, Maximilian M.
Emmerich, Maximilian
Scheuer, Claudia
Hans, Sandra
Ehnert, Sabrina
Nüssler, Andreas K.
Herath, Steven C.
Steinestel, Konrad
Menger, Michael D.
Histing, Tina
Laschke, Matthias W.
Language: English
Title: International Journal of Molecular Sciences
Volume: 25
Issue: 2
Publisher/Platform: MDPI
Year of Publication: 2024
Free key words: mice
fracture healing
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Fracture healing in the aged is associated with a reduced healing capacity, which often results in delayed healing or non-union formation. Many factors may contribute to this deterioration of bone regeneration, including a reduced ‘angiogenic trauma response’. The phosphodiesterase3 (PDE-3) inhibitor cilostazol has been shown to exert pro-angiogenic and pro-osteogenic effects in preclinical studies. Therefore, we herein analyzed in a stable closed femoral fracture model whether this compound also promotes fracture healing in aged mice. Forty-two aged CD-1 mice (age: 16–18 months) were daily treated with 30 mg/kg body weight cilostazol (n = 21) or vehicle (control, n = 21) by oral gavage. At 2 and 5 weeks after fracture, the femora were analyzed by X-ray, biomechanics, micro-computed tomography (µCT), histology, immunohistochemistry, and Western blotting. These analyses revealed a significantly increased bending stiffness at 2 weeks (2.2 ± 0.4 vs. 4.3 ± 0.7 N/mm) and an enhanced bone formation at 5 weeks (4.4 ± 0.7 vs. 9.1 ± 0.7 mm3 ) in cilostazol-treated mice when compared to controls. This was associated with a higher number of newly formed CD31-positive microvessels (3.3 ± 0.9 vs. 5.5 ± 0.7 microvessels/HPF) as well as an elevated expression of phosphoinositide-3-kinase (PI3K) (3.6 ± 0.8 vs. 17.4 ± 5.5-pixel intensity × 104 ) and runt-related transcription factor (RUNX)2 (6.4 ± 1.2 vs. 18.2 ± 2.7-pixel intensity × 104 ) within the callus tissue. These findings indicate that cilostazol accelerates fracture healing in aged mice by stimulating angiogenesis and the expression of PI3K and RUNX2. Hence, cilostazol may represent a promising compound to promote bone regeneration in geriatric patients.
DOI of the first publication: 10.3390/ijms25020755
URL of the first publication:
Link to this record: urn:nbn:de:bsz:291--ds-415069
ISSN: 1422-0067
Date of registration: 29-Jan-2024
Faculty: M - Medizinische Fakultät
Department: M - Chirurgie
Professorship: M - Prof. Dr. Michael D. Menger
M - Prof. Dr. Tim Pohlemann
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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