Role of the HIF‑1α/SDF‑1/CXCR4 signaling axis in accelerated fracture healing after craniocerebral injury

Xue, Yuan; Li, Zhikun; Wang, Yi; Zhu, Xiaodong; Hu, Ruixi; Xu, Wei

doi:10.3892/mmr.2020.11361

Cited by 15 publications

(14 citation statements)

References 37 publications

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“…The SDF-1 could recruit mesenchymal stem cells and participate in endochondral bone repair ( 54 ). Knockdown of HIF-1α repressed mesenchymal stem cell migration by the blocking of the SDF-1/CXCR4 signaling ( 55 ). In the present study, the expression of SDF-1 and CXCR4 was increased along with the HIF-1α at the callosum region of the CIHH treatment rats, indicating that CIHH may contribute to the bone formation by HIF-1α mediated activation of the SDF-1/CXCR4 signaling.…”

Section: Discussionmentioning

confidence: 99%

Chronic Intermittent Hypobaric Hypoxia Enhances Bone Fracture Healing

et al. 2021

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The effect of chronic intermittent hypobaric hypoxia (CIHH) on bone fracture healing is not elucidated. The present study aimed to investigate the role of CIHH on bone fracture healing and the mechanism. The Sprague-Dawley rats were randomly divided into the CIHH group and control group and monitored for 2, 4, or 8 weeks after femoral fracture surgery. Bone healing efficiency was significantly increased in the CIHH group as evidenced by higher high-density bone volume fractions, higher bone mineral density, higher maximum force, and higher stiffness. Histologically, the CIHH group exhibited superior bone formation, endochondral ossification, and angiogenic ability compared with the control group. The expression of HIF-1α and its downstream signaling proteins VEGF, SDF-1/CXCR4 axis were increased by the CIHH treatment. Moreover, the expression of RUNX2, osterix, and type I collagen in the callus tissues were also up-regulated in the CIHH group. In conclusion, our study demonstrated that CIHH treatment improves fracture healing, increases bone mineral density, and increases bone strength via the activation of HIF-1α and bone production-related genes.

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Section: Discussionmentioning

confidence: 99%

Chronic Intermittent Hypobaric Hypoxia Enhances Bone Fracture Healing

et al. 2021

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“…However, bone formation is not only affected by bone materials, but also by O2 concentration. Indeed, hypoxic environments can promote bone formation and bone healing ( Xue et al, 2020 ; Yu et al, 2020 ). Therefore, in the present study, we explored the activities of osteoblasts on the surface of different bioactive titanium implants under normoxic and hypoxic conditions.…”

Section: Discussionmentioning

confidence: 99%

Impact of High-Altitude Hypoxia on Early Osseointegration With Bioactive Titanium

Wang

Zhang

et al. 2021

Front. Physiol.

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Nowadays, the bone osseointegration in different environments is comparable, but the mechanism is unclear. This study aimed to investigate the osseointegration of different bioactive titanium surfaces under normoxic or high-altitude hypoxic environments. Titanium implants were subjected to one of two surface treatments: (1) sanding, blasting, and acid etching to obtain a rough surface, or (2) extensive polishing to obtain a smooth surface. Changes in the morphology, proliferation, and protein expression of osteoblasts on the rough and smooth surfaces were examined, and bone formation was studied through western blotting and animal-based experiments. Our findings found that a hypoxic environment and rough titanium implant surface promoted the osteogenic differentiation of osteoblasts and activated the JAK1/STAT1/HIF-1α pathway in vitro. The animal study revealed that following implant insertion in tibia of rabbit, bone repair at high altitudes was slower than that at low altitudes (i.e., in plains) after 2weeks; however, bone formation did not differ significantly after 4weeks. The results of our study showed that: (1) The altitude hypoxia environment would affect the early osseointegration of titanium implants while titanium implants with rough surfaces can mitigate the effects of this hypoxic environment on osseointegration, (2) the mechanism may be related to the activation of JAK1/STAT1/HIF-1α pathway, and (3) our results suggest the osteogenesis of titanium implants, such as oral implants, is closely related to the oxygen environment. Clinical doctors, especially dentists, should pay attention to the influence of hypoxia on early osseointegration in patients with high altitude. For example, it is better to choose an implant system with rough implant surface in the oral cavity of patients with tooth loss at high altitude.

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“…HIF-1α is a transcriptional factor that can be regulated by a variety of signalling pathways, and Erk1/2 pathway is one of them (R. M. Liu, Xu, Chen, Feng, & Xie, 2020). In cancer cells, the HIF-1α is overexpressed, which regulates tumour survival-related genes, such as CXCL12 andCXCR4 (Gola et al, 2020;Xue et al, 2020). It was in line with the results of the current study that sevoflurane upregulated Erk1/2 signalling pathway, and HIF-1α, CXCL12 and CXCR4 expressions, while propofol downregulated these molecular entities.…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane but not propofol enhances ovarian cancer cell malignancy through regulating cellular metabolic and signalling mechanisms

Wang

Liu

et al. 2021

Preprint

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Background and Purpose: Surgery remains the first-line treatment of ovarian cancer. However, perioperative risk factors including the choice of anaesthetics may influence its recurrence after surgery. In the current study, it was hypothesised that inhalational anaesthetic sevoflurane and intravenous anaesthetic propofol might affect cancer cellular metabolism and signalling, which might interfere the malignancy of ovarian cancer cells. Experimental Approach: Cultured ovarian cancer cells were exposed to 2.5% sevoflurane or administered with 4 μg/mL propofol for 2 hours followed by 24 hours recovery. Their cell viability, proliferation, migration and invasion were assessed using cell counting kit-8, Ki-67 staining, wound healing and Transwell assay. Cellular signalling biomarkers were measured using immunofluorescent staining and/or Western blot. Cultured media were collected for 1H-NMR spectroscopy-based metabolomics analysis. Key Results: The cell viability, proliferation, migration, and invasion of ovarian cancer cells were enhanced by sevoflurane but suppressed by propofol. Sevoflurane increased the GLUT1, MPC1, GLUD1, p-Erk1/2, and HIF-1α expressions but decreased the PEDF expression. In contrast to the sevoflurane treatment, the “mirror changes” of these cellular markers were observed with propofol. Sevoflurane increased levels of isopropanol but decreased glucose and glutamine levels in the media, but the opposite changes of those metabolites were found after propofol treatment. Conclusion and Implications: These data indicated that unlike propofol, sevoflurane enhanced ovarian cancer cell metabolism and activated PEDF/Erk/HIF-1α cellular signalling pathway, suggesting that sevoflurane might have pro-tumour property but propofol might afford an anti-tumour property. The translational value of this work warrants further study.

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Role of the HIF‑1α/SDF‑1/CXCR4 signaling axis in accelerated fracture healing after craniocerebral injury

Cited by 15 publications

References 37 publications

Chronic Intermittent Hypobaric Hypoxia Enhances Bone Fracture Healing

Chronic Intermittent Hypobaric Hypoxia Enhances Bone Fracture Healing

Impact of High-Altitude Hypoxia on Early Osseointegration With Bioactive Titanium

Sevoflurane but not propofol enhances ovarian cancer cell malignancy through regulating cellular metabolic and signalling mechanisms

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