Evaluating effects of deferoxamine in a rat tibia critical bone defect model

Grewal, Bikramjit S.; Keller, B; Weinhold, Paul S.; Dahners, Laurence E.

doi:10.1016/j.jor.2013.12.005

Cited by 19 publications

(20 citation statements)

References 14 publications

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“…The activation of HIF-1α in osteoblasts via the disruption of its degradation pathway produced robust bone modelling early in development7. Consistent with the “promoting osteogenesis by enhancing angiogenesis” theory, HIF-1α pathway activators (DMOG or DFO) or mesenchymal stem cells overexpressing HIF-1α have been shown to improve fracture and bone defect healing35363738394041. HIF-1α that binds to the aryl hydrocarbon receptor nuclear translocator (ARNT) is known as HIF-1β.…”

Section: Discussionmentioning

confidence: 95%

Protective effect of salidroside against bone loss via hypoxia-inducible factor-1α pathway-induced angiogenesis

Li¹,

Jin

et al. 2016

Sci Rep

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Hypoxia-inducible factor (HIF)-1α plays a critical role in coupling angiogenesis with osteogenesis during bone development and regeneration. Salidroside (SAL) has shown anti-hypoxic effects in vitro and in vivo. However, the possible roles of SAL in the prevention of hypoxia-induced osteoporosis have remained unknown. Two osteoblast cell lines, MG-63 and ROB, were employed to evaluate the effects of SAL on cell viability, apoptosis, differentiation and mineralization in vitro. Rats subjected to ovariectomy-induced bone loss were treated with SAL in vivo. Our results showed that pre-treatment with SAL markedly attenuated the hypoxia-induced reductions in cell viability, apoptosis, differentiation and mineralization. SAL down-regulated HIF-1α expression and inhibited its translocation; however, SAL increased its transcriptional activity and, consequently, up-regulated vascular endothelial growth factor (VEGF). In vivo studies further demonstrated that SAL caused decreases in the mineral, alkaline phosphatase (ALP), and BGP concentrations in the blood of ovariectomized (OVX) rats. Moreover, SAL improved the trabecular bone microarchitecture and increased bone mineral density in the distal femur. Additionally, SAL administration partially ameliorated this hypoxia via the HIF-1α-VEGF signalling pathway. Our results indicate that SAL prevents bone loss by enhancing angiogenesis and osteogenesis and that these effects are associated with the activation of HIF-1α signalling.

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Section: Discussionmentioning

confidence: 95%

Protective effect of salidroside against bone loss via hypoxia-inducible factor-1α pathway-induced angiogenesis

Li¹,

Jin

et al. 2016

Sci Rep

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“…; Grewal et al. ) although its effectiveness against unloading‐induced reduction in bone healing has not been confirmed. Furthermore, DFO remains effective in improving detriments of angiogenesis and osteogenesis in non–weight bearing bones such as mandible (Farberg et al.…”

Section: Discussionmentioning

confidence: 99%

“…; Grewal et al. ) although its effectiveness against unloading‐induced reduction in bone healing has not been experimentally confirmed. Using a contrast agent containing zirconium dioxide particles (ZrCA) for vascular casting and taking advantage of its absorption discontinuity, three‐dimensional images of angiogenic vessels and newly formed bone were acquired by synchrotron radiation‐based subtraction microcomputed tomography (SRS μ CT), a method that was established in a previous study from our group (Matsumoto et al.…”

Section: Introductionmentioning

confidence: 99%

Stimulating angiogenesis mitigates the unloading-induced reduction in osteogenesis in early-stage bone repair in rats

Matsumoto

Sato

2015

Physiol Rep

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Accelerating fracture healing during bed rest allows early mobilization and avoids prolonged fracture healing times. We tested the hypothesis that stimulating angiogenesis with deferoxamine (DFO) mitigates the unloading-induced reduction in early-stage bone repair. Rats aged 12 weeks were subjected to cortical drilling on their tibial diaphysis under anesthesia and treated with hindlimb unloading (HU), HU and DFO administration (DFOHU), or weight bearing (WB) for 5 or 10 days (HU5/10, DFOHU5/10, WB5/10; n = 8 per groups) until sacrifice for vascular casting with a zirconium dioxide-based contrast agent. Taking advantage of its absorption discontinuity at the K-absorption edge, vascular and bone images in the drill-hole defects were acquired by synchrotron radiation subtraction CT. Bone repair was reduced in HU rats. The bone volume fraction (B.Vf) was 88% smaller in HU5 and 42% smaller in HU10 than in WB5/10. The bone segment densities (B.Seg) were 97% smaller in HU5 and 141% larger in HU10 than in WB5/10, and bone thickness (B.Th) was 38% smaller in HU10 than in WB10. The vascular volume fraction (V.Vf) was 35% and the mean vessel diameter (V.D) was 13% smaller in HU10 than in WB10. When compared according to categorized vessel sizes, V.Vf in the diameter ranges 20–30, 30–40, and >40 μm were smaller in HU10 than in WB10, and V.Seg in the diameter range >40 μm was smaller in HU10 than in WB10. In contrast, there was no difference in B.Vf between DFOHU5/10 and WB5/10 and in V.Vf between DFOHU10 and WB10, though B.Seg remained 86% smaller in DFOHU5 and 94% larger in DFOHU10 than in WB5/10, and B.Th and V.D were 23% and 14% lower in DFOHU10 than in WB10. Vessel size-specific V.Vf in the diameter ranges 10–20 and 20–30 μm was larger in DFOHU5 than in HU5. In conclusion, the enhanced angiogenic ingrowth mitigates the reduction in bone repair during mechanical unloading.

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“…DFO bolsters bone repair in distraction osteogenesis, transverse fractures, radiated fractures, and steroid‐induced osteonecrosis of the femoral head . Furthermore, DFO promotes healing in various bone defect models . A recent study demonstrates that DFO prevents bone loss in aged mice by promoting osteogenesis and angiogenesis in a systemic, nonlocalized manner …”

Section: Introductionmentioning

confidence: 99%

“…33,[44][45][46][47][48][49][50] Furthermore, DFO promotes healing in various bone defect models. [51][52][53] A recent study demonstrates that DFO prevents bone loss in aged mice by promoting osteogenesis and angiogenesis in a systemic, nonlocalized manner. 54 The present study is the first to investigate whether DFO can reverse the reduced bone regeneration capacity in osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

Deferoxamine released from poly(lactic‐co‐glycolic acid) promotes healing of osteoporotic bone defect via enhanced angiogenesis and osteogenesis

Jia

Chen

Kang

et al. 2016

J Biomedical Materials Res

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The regeneration capacity of osteoporotic bones is generally lower than that of normal bones. Current methods of osteoporotic bone defect treatment are not always satisfactory. Recent studies demonstrate that activation of the hypoxia inducible factor-1α (HIF-1α) pathway, by genetic methods or hypoxia-mimicking agents, could accelerate bone regeneration. However, little is known as to whether modulating the HIF-1α pathway promotes osteoporotic defect healing. To address this problem in the present study, we first demonstrated that HIF-1α and vascular endothelial growth factor expression levels are lower in osteoporotic bones than in normal bones. Second, we loaded poly(Lactic-co-glycolic acid) (PLGA) with the hypoxia-mimetic agent deferoxamine (DFO). DFO released from PLGA had no significant effect on the proliferation of mesenchymal stem cells (MSCs); however, DFO did enhance the osteogenic differentiation of MSCs. In addition, DFO upregulated the mRNA expression levels of angiogenic factors in MSCs. Endothelial tubule formation assays demonstrate that DFO promoted angiogenesis in human umbilical vein endothelial cells. Third, untreated PLGA scaffolds (PLGA group) or DFO-containing PLGA (PLGA + DFO group) were implanted into critically sized osteoporotic femur defects in ovariectomized rats. After treatment periods of 14 or 28 days, micro-CT, histological, CD31 immunohistochemical, and dynamic bone histomorphometric analyses showed that DFO dramatically stimulated bone formation and angiogenesis in a critically sized osteoporotic femur defect model. Our in vitro and in vivo results demonstrate that DFO may promote the healing of osteoporotic bone defects due to enhanced angiogenesis and osteogenesis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2515-2527, 2016.

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Evaluating effects of deferoxamine in a rat tibia critical bone defect model

Cited by 19 publications

References 14 publications

Protective effect of salidroside against bone loss via hypoxia-inducible factor-1α pathway-induced angiogenesis

Protective effect of salidroside against bone loss via hypoxia-inducible factor-1α pathway-induced angiogenesis

Stimulating angiogenesis mitigates the unloading-induced reduction in osteogenesis in early-stage bone repair in rats

Deferoxamine released from poly(lactic‐co‐glycolic acid) promotes healing of osteoporotic bone defect via enhanced angiogenesis and osteogenesis

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