Effect of Dual Treatment with SDF-1 and BMP-2 on Ectopic and Orthotopic Bone Formation

Lee, Chang-Hwan; Jin, Myoung Uk; Jung, Hyun-Kyo; Lee, Jung-Tae; Kwon, Tae-Geon

doi:10.1371/journal.pone.0120051

Cited by 26 publications

(20 citation statements)

References 38 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, a recent study by Lee et al found no synergistic effect of BMP‐2 and SDF‐1α on bone regeneration using a critical size murine calvarial bone defect and collagen sponges as scaffolds . The authors used SDF‐1α doses between 0.1 and 1 µg, which is 10 to 100 times lower than the dose we used in the current study.…”

Section: Discussioncontrasting

confidence: 69%

See 1 more Smart Citation

The effect of SDF‐1α on low dose BMP‐2 mediated bone regeneration by release from heparinized mineralized collagen type I matrix scaffolds in a murine critical size bone defect model

Zwingenberger

Langanke

Vater

et al. 2016

J Biomedical Materials Res

View full text Add to dashboard Cite

The treatment of critical size bone defects represents a challenge. The growth factor bone morphogenetic protein 2 (BMP-2) is clinically established but has potentially adverse effects when used at high doses. The aim of this study was to evaluate if stromal derived factor-1 alpha (SDF-1α) and BMP-2 released from heparinized mineralized collagen type I matrix (MCM) scaffolds have a cumulative effect on bone regeneration. MCM scaffolds were functionalized with heparin, loaded with BMP-2 and/or SDF-1α and implanted into a murine critical size femoral bone defect (control group, low dose BMP-2 group, low dose BMP-2 + SDF-1α group, and high dose BMP-2 group). After 6 weeks, both the low dose BMP-2 + SDF-1α group (5.8 ± 0.6 mm³, p = 0.0479) and the high dose BMP-2 group (6.5 ± 0.7 mm³, p = 0.008) had a significantly increased regenerated bone volume compared to the control group (4.2 ± 0.5 mm³). There was a higher healing score in the low dose BMP-2 + SDF-1α group (median grade 8; Q1-Q3 7-9; p = 0.0357) than in the low dose BMP-2 group (7; Q1-Q3 5-9) histologically. This study showed that release of BMP-2 and SDF-1α from heparinized MCM scaffolds allows for the reduction of the applied BMP-2 concentration since SDF-1α seems to enhance the osteoinductive potential of BMP-2. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2126-2134, 2016.

show abstract

Section: Discussioncontrasting

confidence: 69%

“…using a critical size murine calvarial bone defect and collagen sponges as scaffolds. 24 The authors used SDF-1a doses between 0.1 and 1 mg, which is 10 to 100 times lower than the dose we used in the current study. This might be an explanation for the missing cumulative effect.…”

Section: Discussionmentioning

confidence: 90%

The effect of SDF‐1α on low dose BMP‐2 mediated bone regeneration by release from heparinized mineralized collagen type I matrix scaffolds in a murine critical size bone defect model

Zwingenberger

Langanke

Vater

et al. 2016

J Biomedical Materials Res

View full text Add to dashboard Cite

show abstract

“…The dose we chose (1 μg of BMP2) should cause bone formation in vivo. 26 , 27 , 28 , 29 , 30 , 31 To further understand the mechanism causing no bone formation in this group, we performed a BMP2 release experiment from PLLA. We loaded 1 μg of BMP2 into a scaffold, incubated it in PBS, and collected the solution at a different time point.…”

Section: Discussionmentioning

confidence: 99%

One-Step Fabrication of Bone Morphogenetic Protein-2 Gene-Activated Porous Poly-L-Lactide Scaffold for Bone Induction

Xue

Lin

Bean

et al. 2017

Molecular Therapy - Methods & Clinical Development

View full text Add to dashboard Cite

Bone morphogenetic protein 2 (BMP2) is an efficacious inducer for the osteogenesis of mesenchymal stem cells (MSCs). Conventional applications of BMP2 have involved either the direct incorporation of BMP2 protein or ex vivo BMP2 gene transfer into stem cells prior to their transplantation. These approaches are able to promote bone formation to some extent; however, they are hampered by either the lack of stability and sustainability of BMP2 protein or the time-consuming and cost-prohibitive in vitro cell culture procedure. To overcome these limitations, we have developed a gene-activated poly-L-lactide acid (PLLA) scaffold with the encapsulation of recombinant adeno-associated viral (AAV) vector encoding a full-length cDNA of human BMP2 using an ice-based microparticle porogenization method that was recently developed. Results showed continuous release of AAV particles from the micropores of scaffolds for up to 1 week, subsequently transducing embedded human MSCs and producing functional BMP2. MSCs within scaffolds underwent efficacious osteogenesis, on the basis of osteoinductive gene expression and osteogenic differentiation, which resulted in robust new bone formation in vivo at 4 weeks. These findings show the potential of the technology toward developing clinical applications of a rapid, cost-effective, and potentially point-of-care approach for the repair of bone defects.

show abstract

“…To further explore if RUNX2 is directly related to Rg1-induced angiogenesis, we performed a tube formation assay. This system mimics the reorganization of endothelial cells into a three-dimensional network during angiogenesis [ 28 , 29 ]. Since the number of branch points reflects angiogenic activity in endothelial cells, we observed the capillary structures of HUVECs under various treatments.…”

Section: Resultsmentioning

confidence: 99%

MiR-23a targets RUNX2 and suppresses ginsenoside Rg1-induced angiogenesis in endothelial cells

Guo

Liu

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Rg1 is a predominant protopanaxatriol-type of ginsenoside found in Panax ginseng, and it has been shown to have anti-cancer effects in multiple types of cancer cells. However, Rg1 also induces the expression of proangiogenic factors, such as vascular endothelial growth factor (VEGF-A), in endothelial cells. Unfortunately, angiogenesis positively correlates with cancer development. In this study, we identified RUNX2 as a regulator of ginsenoside Rg1-induced angiogenesis for the first time. We found that RUNX2 was directly targeted and regulated by miR-23a. Additionally, miR-23a was shown to inhibit angiogenesis in both human umbilical vein endothelial cells (HUVECs) and in zebrafish. Furthermore, a decrease in RUNX2 expression resulted in translational repression of VEGF-A in HUVECs. Taken together, this study identified a MiR-23a/RUNX2/VEGF-A pathway in angiogenesis and shed light on the molecular mechanism of Rg1-induced angiogenesis. Thus, RUNX2 might be a potential therapeutic target in Rg1-mediated angiogenesis in cancer.

show abstract

Effect of Dual Treatment with SDF-1 and BMP-2 on Ectopic and Orthotopic Bone Formation

Cited by 26 publications

References 38 publications

The effect of SDF‐1α on low dose BMP‐2 mediated bone regeneration by release from heparinized mineralized collagen type I matrix scaffolds in a murine critical size bone defect model

The effect of SDF‐1α on low dose BMP‐2 mediated bone regeneration by release from heparinized mineralized collagen type I matrix scaffolds in a murine critical size bone defect model

One-Step Fabrication of Bone Morphogenetic Protein-2 Gene-Activated Porous Poly-L-Lactide Scaffold for Bone Induction

MiR-23a targets RUNX2 and suppresses ginsenoside Rg1-induced angiogenesis in endothelial cells

Contact Info

Product

Resources

About