Effect of rhBMP–2 sustained–release nanocapsules on the ectopic osteogenesis process in Sprague–Dawley rats

Lai, Renfa; Li, Ze–Jian; Zhou, Zhen; Feng, Zhiqiang; Zhao, Qingtong

doi:10.1016/s1995-7645(13)60157-1

Cited by 20 publications

(13 citation statements)

References 13 publications

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“…The hMSCs were induced under OM for 1 week before the in vivo study. The cells were resuspended and incubated with 7 mm × 5 mm × 2 mm Bio‐Oss Collagen (Geistlich, GEWO GmbH, Baden‐Baden, Germany, http://www.geistlich-na.com/en-us/) scaffolds for 1 hour at 37°C followed by centrifugation at 150 g for 5 minutes, and then implanted subcutaneously on the back of 5‐week‐old BALB/c homozygous nude (nu/nu) mice (five mice per group), as described previously . Implants were harvested after 8 weeks and fixed in 4% paraformaldehyde.…”

Section: Methodsmentioning

confidence: 99%

“…Image slices were then reconstructed using micro‐CT image analysis software (Inveon Research Workplace). The three‐dimensional reconstruction and volume quantification of the ectopic bone were performed using standardized thresholds as described previously . The region of interest was selected, and the lower and upper threshold values for bone were set.…”

Section: Methodsmentioning

confidence: 99%

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Long Noncoding RNA H19 Promotes Osteoblast Differentiation Via TGF-β1/Smad3/HDAC Signaling Pathway by Deriving miR-675

et al. 2015

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Long noncoding RNAs (lncRNAs) are emerging as important regulatory molecules at the transcriptional and post-transcriptional levels and may play essential roles in the differentiation of human bone marrow mesenchymal stem cell (hMSC). However, their roles and functions remain unclear. Here, we showed that lncRNA H19 was significantly upregulated after the induction of osteoblast differentiation. Overexpression of H19 promoted osteogenic differentiation of hMSCs in vitro and enhanced heterotopic bone formation in vivo, whereas knockdown of H19 inhibited these effects. Subsequently, we found that miR-675, encoded by exon1 of H19, promoted osteoblast differentiation of hMSCs and was partially responsible for the pro-osteogenic effect of H19. Investigating the underlying mechanism, we demonstrated that H19/miR-675 inhibited mRNA and protein expression of transforming growth factor-b1 (TGF-b1). The downregulation of TGF-b1 subsequently inhibited phosphorylation of Smad3. Meanwhile, H19/miR-675 downregulated the mRNA and protein levels of histone deacetylase (HDAC) 4/5, and thus increased osteoblast marker gene expression. Taken together, our results demonstrated that the novel pathway H19/miR-675/TGF-b1/Smad3/HDAC regulates osteogenic differentiation of hMSCs and may serve as a potential target for enhancing bone formation in vivo. STEM CELLS 2015;33:3481-3492 SIGNIFICANCE STATEMENTLong noncoding RNAs (lncRNAs) are emerging as important regulatory molecules in biology control and pathology. However, their roles and functions in osteogenic differentiation of mesenchymal stem cell (MSC) remain unclear. Our studies provide important insights into the prodifferentiation effect of lncRNA H19 in osteogenesis both in vitro and in vivo. miR-675 is partially responsible for this pro-osteogenic effect of H19 via the transforming growth factor-b1 (TGF-b1)/Smad3/histone deacetylase (HDAC) pathway. These findings provide important clues for understanding the role of lncRNA-miRNA-mRNA functional network in osteogenic differentiation, and would be helpful in developing stem cell-based therapy for bone defect.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Long Noncoding RNA H19 Promotes Osteoblast Differentiation Via TGF-β1/Smad3/HDAC Signaling Pathway by Deriving miR-675

et al. 2015

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“…TNF-α, interleukins, interferon gamma (IFNγ), prostaglandins]. These "nanosystems" have been shown to regulate recruitment, migration and differentiation of bone cells, and, as in the in vivo conditions, to favor cell survival and to guide bone healing [228][229][230][231]. At the nanometer scale, it becomes possible to regulate cell interactions by means of specific proteins, so mimicking the nanocomposite structure of bone tissue.…”

Section: Nanoscalementioning

confidence: 99%

From the macroscale to nanostructures: can tissue engineering recreate bone features?

Steimberg¹,

Mazzoleni²

2016

Nanomaterials and Regenerative Medicine

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“…After this, GF dose–response effects became all the more crucial (Shields et al, 2006 ), and it became evident that adverse outcomes could have been avoided with the controlled, localized release of rhBMP-2. It was determined that burst release and widespread tissue exposure to GFs, together with an early dissipation from the implantation site (e.g., with irrigation, bleeding, and edema) were not ideal pharmacokinetics for tissue regeneration (Lai et al, 2013 ). Furthermore, it has become clear that the first-order release of a single bioactive molecule is not sufficient to mimic the complex biochemical gradients present at a specific stage of tissue regeneration (Wang et al, 2013 ; Minardi et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Patterning Biomaterials for the Spatiotemporal Delivery of Bioactive Molecules

Minardi

Taraballi

Pandolfi

et al. 2016

Front. Bioeng. Biotechnol.

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The aim of tissue engineering is to promote the repair of functional tissues. For decades, the combined use of biomaterials, growth factors (GFs), and stem cells has been the base of several regeneration strategies. Among these, biomimicry emerged as a robust strategy to efficiently address this clinical challenge. Biomimetic materials, able to recapitulate the composition and architecture of the extracellular matrix, are the materials of choice, for their biocompatibility and higher rate of efficacy. In addition, it has become increasingly clear that restoring the complex biochemical environment of the target tissue is crucial for its regeneration. Toward this aim, the combination of scaffolds and GFs is required. The advent of nanotechnology significantly impacted the field of tissue engineering by providing new ways to reproduce the complex spatial and temporal biochemical patterns of tissues. This review will present the most recent approaches to finely control the spatiotemporal release of bioactive molecules for various tissue engineering applications.

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Effect of rhBMP–2 sustained–release nanocapsules on the ectopic osteogenesis process in Sprague–Dawley rats

Abstract: The slow-release effect of rhBMP-2/cs sustained-release capsules can significantly promote ectopic osteogenesis. Its bone formation effect is better than that of rhBMP-2 burst-release group.

Cited by 20 publications

References 13 publications

Long Noncoding RNA H19 Promotes Osteoblast Differentiation Via TGF-β1/Smad3/HDAC Signaling Pathway by Deriving miR-675

Long Noncoding RNA H19 Promotes Osteoblast Differentiation Via TGF-β1/Smad3/HDAC Signaling Pathway by Deriving miR-675

From the macroscale to nanostructures: can tissue engineering recreate bone features?

Patterning Biomaterials for the Spatiotemporal Delivery of Bioactive Molecules

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