Level D· Scientific groundwork from lab and animal studiesAnimal StudyEurope PMCOpen access

GNAS1 and PHD2 short-interfering RNA support bone regeneration in vitro and in an in vivo sheep model

Ríos CN., Skoracki RJ., Mathur AB.

Animal Study with a reported sample of 3, published in Clin Orthop Relat Res (2012) — summary generated from the PubMed abstract.

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Level D· Scientific groundwork from lab and animal studiesEvidence level of this study

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

  • Level A · Stronger Clinical Evidence
  • Level B · Emerging clinical evidence with positive signals
  • Level C · Early human research exploring benefits
  • Level D · Scientific groundwork from lab and animal studies
  • Emerging · Emerging topic under active research
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This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.

Study type
Animal Study
Journal
Clin Orthop Relat Res (2012)
Reported sample size
3
Source database
Europe PMC
PMID
22833384
PMCID
PMC3830105
DOI
10.1007/s11999-012-2475-4
Citations
29

Abstract (original English)

Background Our ability to guide cells in biomaterials for in vivo bone repair is limited and requires novel strategies. Short-interfering RNA (siRNA) allows the regulation of multiple cellular pathways. Core binding factor alpha 1 (Cbfa1) and hypoxia-inducible factor 1 (HIF-1) pathways can be modulated to direct bone formation via siRNA against guanine nucleotide-binding protein alpha-stimulating activity polypeptide 1 (siGNAS1) and prolyl hydroxylase domain-containing protein 2 (siPHD2), respectively. Questions/purposes We determined whether the administration of siGNAS1 and siPHD2 in mesenchymal stem cells (MSCs) promotes osteogenic phenotype, the dose-dependent effects of siGNAS1 on MSC differentiation to osteogenic phenotype, and whether the two siRNAs promote bone formation in vivo. Methods siRNAs were administered to MSCs at Day 0, and protein expression of bone-specific markers was assessed at Days 1, 2, and 4 (n = 3/group/time point). In an in vivo model using seven sheep, chambers containing silk fibroin-chitosan (SFCS) scaffolds with siRNA were implanted over the periosteum and harvested at Days 7, 21, 36, and 70 (n = 4/group/time point, except at Day 70 [n = 2]) to assess bone formation. Results siGNAS1 promoted collagen I and osteopontin expression, whereas siPHD2 had no effect in vitro. Dose-dependent effects of siGNAS1 on ALP expression were maximal at Day 1 for 1

What this study does not prove

  • • This study does not prove SVF is an approved treatment or a replacement for standard care.
  • • This is preclinical work; animal or laboratory results cannot be applied to humans.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

How we grade evidence
PeriosteumCells, CulturedMesenchymal Stem CellsAnimalsSheepHumansCollagen Type IGTP-Binding Protein alpha Subunits, GsAlkaline PhosphataseProcollagen-Proline Dioxygenase

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