Role of Sildenafil in Acceleration of Delayed Union Fracture Healing on Sprague-Dawley Rats Model

Kamal, Achmad Fauzi; Kurniawan, Aryadi; Kodrat, Evelina

doi:10.9734/bjmmr/2015/15427

Cited by 5 publications

(5 citation statements)

References 24 publications

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“…Therefore, further studies about NO/cGMP/PKG pathway need to be further studied. Third, sildenafil can accelerate fracture healing including delayed union 28 , 29 and attenuate apoptosis and oxidative stress, 30 which were greatly connected with osteonecrosis; however, our study did not involve those.…”

Section: Discussionmentioning

confidence: 87%

Sildenafil improves blood perfusion in steroid-induced avascular necrosis of femoral head in rabbits via a protein kinase G-dependent mechanism

Song¹,

Ni²,

Jiang³

et al. 2017

Acta Orthopaedica et Traumatologica Turcica

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ObjectiveThe aim of the study were to evaluate the effect of sildenafil against avascular necrosis of femoral head (ANFH) in a rabbit model, and to study the role of protein kinase G (PKG) pathway and vascular endothelial growth factor (VEGF) in ANFH.MethodsThree weeks after inducing ANFH with methylprednisolone injection, 45 female adult New Zealand white rabbits were divided into three groups and treated as follows: group SI received daily intraperitoneal sildenafil with a dose of 10 mg/kg per day; group SD received daily sildenafil identically to group SI plus auricular vein injection DT3 (a specific PKG inhibitor); group NS received only normal saline. The blood perfusion function in the femoral head was measured by perfusion MRI and ink artery infusion. Bilateral femora heads were examined histopathologically for the presence of osteonecrosis; VEGF of tissue was examined by Western blot analysis; cGMP level and PKG activity were also measured.ResultsThe incidence of ANFH in SI group was significantly lower than that observed in NS and SD groups (p < 0.05). VEGF in SI group was increased compared to NS group. cGMP level and PKG activity were also significantly different between NS and SI group (p < 0.05). However, these effects of sildenafil in SD group were all markedly inhibited by the administration of DT3 compared to SI group.ConclusionSildenafil appear to increase the perfusion of femoral head by up-regulating VEGF through PKG pathway. The increased perfusion of femoral head could prevent ANFH.

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Section: Discussionmentioning

confidence: 87%

Sildenafil improves blood perfusion in steroid-induced avascular necrosis of femoral head in rabbits via a protein kinase G-dependent mechanism

Song¹,

Ni²,

Jiang³

et al. 2017

Acta Orthopaedica et Traumatologica Turcica

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“…The fracture site was exposed and 5 mm of the periosteum was stripped on each side to create the delayed union model. A 1.2 mm diameter K-wire was inserted into the femoral canal in a retrograde fashion through the knee joint to stabilize the fracture with the use of a motordriven drill (Fauzi et al, 2015). Lastly, soft tissues were sutured with absorbable sutures at the end of the procedure.…”

Section: Rats Fracture Modelmentioning

confidence: 99%

The Effect of Pulsed Electromagnetic Field Exposure on Fracture Healing Through the Wnt Signal Pathway

Umiatin

Dilogo²,

Sari³

et al. 2020

OnLine Journal of Biological Sciences

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Pulsed Electromagnetic Fields (PEMF) is reported to encourage the healing of nonunion fractures. However, the mechanism by which this occurs is still not known. Wnt signaling pathways are believed to be important signaling pathways in bone formation. This study will evaluate the healing of delayed union femur fracture, given PEMF exposure. 48 Spraque Dawley rats were fracturized at the left femoral shaft. These rats were randomized into two groups: A control group (24 rats) and the PEMF group (24 rats). The PEMF group was given PEMF exposure of 1.6 mT, with a frequency of 50 Hz for 4 h every day for 5, 10, 18 and 28 days, while the control group was not given PEMF exposure. Consequently, on days 5, 10, 18 and 28 days after fracture, 6 rats from each group were sacrificed. Callus bone was used for histological and RT-PCR examination on the expression of Wnt10b, Wnt5a and β-catenin. Blood samples were taken to examine Alkaline Phosphatase (ALP) activity using the ELISA method. Hematoxylin Eosin (HE) staining results showed that in the initial phase of healing, fibrous tissue in the fracture gap of the PEMF group was less compared to the control group. In the PEMF group, ALP activity increased significantly on day 10. This is thought to be related to an increase in osteoblast activity in a bone matrix formation. Furthermore, RT-PCR examination results showed that Wnt10b, Wnt5a and β-catenin gene expression was higher in the PEMF group compared to the control group. It can be concluded that PEMF exposure is thought to accelerate delayed union fracture healing through the Wnt signal pathway.

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“…Due to a reduction in blood supply following bone or soft tissue injury, the microenvironment surrounding lesions enters a hypoxia state (4). Thus, angiogenesis serves an important role in the process of fracture healing (5,6). Osteogenesis is closely associated with angiogenesis in the formation and repair of bone (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

“…Thus, angiogenesis serves an important role in the process of fracture healing (5,6). Osteogenesis is closely associated with angiogenesis in the formation and repair of bone (5)(6)(7). Vessels carry oxygen and nutrients; however, they also serve a pivotal role in the formation, reshaping and alteration of bone through interactions between osteoblasts, osteocytes or osteoclasts and cytokines in the blood vessels (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

“…Osteogenesis is closely associated with angiogenesis in the formation and repair of bone (5)(6)(7). Vessels carry oxygen and nutrients; however, they also serve a pivotal role in the formation, reshaping and alteration of bone through interactions between osteoblasts, osteocytes or osteoclasts and cytokines in the blood vessels (5)(6)(7). Hypoxia is considered to be an important stimulus in angiogenesis (8); this stimulus is now thought to be achieved by hypoxia inducible factor-1α (HIF-1α) (9).…”

Section: Introductionmentioning

confidence: 99%

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HIF-1-mediated expression of Foxo1 serves an important role in the proliferation and apoptosis of osteoblasts derived from children's iliac cancellous bone

2018

Mol Med Report

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Activation of the transcription factor hypoxia inducible factor‑1α (HIF-1α) is considered critical for the stimulation of osteogenic markers including runt‑related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin, which are closely associated with forkhead boxclass O1 (Foxo1) levels in osteoblasts. The present study explored the associations between HIF‑1α and Foxo1 in the regulation of cell viability, proliferation and apoptosis of osteoblasts. Osteoblasts obtained from children's iliac cancellous bone were used in the present study, which were confirmed by immunofluorescence staining for the osteoblast marker osteocalcin. The results revealed that the levels of reactive oxygen species and apoptosis were markedly increased in cells with knockdown of HIF‑1α. By contrast, these were reduced in response to overexpressed HIF‑1α. In addition, HIF‑1α overexpression significantly stimulated cell viability, which was suppressed by silencing HIF‑1α. HIF‑1α overexpression also significantly increased the transcriptional and translational levels of Foxo1. Conversely, silencing HIF‑1α markedly suppressed the expression levels of Foxo1. Furthermore, silencing HIF‑1α reduced the expression of osteogenic markers, including Runx2, ALP and osteocalcin. Runx2 and ALP expression induced by HIF1α were markedly reversed by Foxo1 small interfering (si)RNA, whereas osteocalcin was not significantly affected by Foxo1 siRNA. Therefore, the cooperation of and interactions between HIF‑1α and Foxo1 may be involved in the regulation of osteoblast markers, and serve a pivotal role in the proliferation and apoptosis of osteoblast. The HIF1α‑induced expression of Runx2 and ALP may be completely dependent on the expression levels of Foxo1, and in turn, osteocalcin may be partially dependent on Foxo1 expression.

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Role of Sildenafil in Acceleration of Delayed Union Fracture Healing on Sprague-Dawley Rats Model

Cited by 5 publications

References 24 publications

Sildenafil improves blood perfusion in steroid-induced avascular necrosis of femoral head in rabbits via a protein kinase G-dependent mechanism

Sildenafil improves blood perfusion in steroid-induced avascular necrosis of femoral head in rabbits via a protein kinase G-dependent mechanism

The Effect of Pulsed Electromagnetic Field Exposure on Fracture Healing Through the Wnt Signal Pathway

HIF-1-mediated expression of Foxo1 serves an important role in the proliferation and apoptosis of osteoblasts derived from children's iliac cancellous bone

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