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HIF/Ca2+/NO/ROS is critical in roxadustat treating bone fracture by stimulating the proliferation and migration of BMSCs
- Source :
- Life Sciences. 264:118684
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Aims Fracture site is regionally hypoxic resulting from vasculature disruption. HIF-1αplays an essential role in fracture repair. This study aims to investigate the influence of FG4592 on the femur fracture of SD rats and the proliferation, migration of BMSCs. Materials and methods After the femoral fracture model was established, computed tomography imaging and histological analyses were used to quantify bone healing and the expression of CD90, HIF-1α, VEGF were observed by means of immunohistochemistry method on Day 10 and Day 20. In addition, CCK-8 assay, transwell, flow cytometric analysis, laser confocal microscopy assay, western blot and rT-PCR were performed to text the proliferation and migration of BMSCs using FG4592. Key findings In vivo, FG4592 facilitated the repair of bone fracture by increasing the number of BMSCs and cartilage formation. In vitro, FG4592 markedly improved the proliferation, migration of BMSCs via upregulation of intracellular Ca2+, NO and concomitant decrease of ROS. Gene silencing of HIF-1α resulted in the opposite phenomenon in BMSCs with the treatment of FG4592. Significance The transplantation of BMSCs is the most promising candidate for the treatment of fracture non-union. We illustrated that FG4592 promoted the proliferation, migration of BMSCs via the HIF/Ca2+/NO/ROS pathway and further accelerated fracture healing. These results provide a deeper understanding for the mechanism of HIF in promoting fracture healing.
- Subjects :
- 0301 basic medicine
Femur fracture
Chemistry
General Medicine
Bone healing
Bone fracture
Femoral fracture
medicine.disease
030226 pharmacology & pharmacy
General Biochemistry, Genetics and Molecular Biology
Transplantation
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
stomatognathic system
Downregulation and upregulation
In vivo
medicine
Cancer research
CD90
General Pharmacology, Toxicology and Pharmaceutics
Subjects
Details
- ISSN :
- 00243205
- Volume :
- 264
- Database :
- OpenAIRE
- Journal :
- Life Sciences
- Accession number :
- edsair.doi...........da2960d5e4a82dbcd76143453a7d649a