ArticleClinical orthopaedics and related research2012
GNAS1 and PHD2 short-interfering RNA support bone regeneration in vitro and in an in vivo sheep model.
Article in Clinical orthopaedics and related research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 39 citations in OpenAlex.
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- The Role of HIF-1α in Bone Regeneration: A New Direction and Challenge in Bone Tissue Engineering.International journal of molecular sciences · 2023Review
- Role of prolyl hydroxylase domain proteins in bone metabolism.Osteoporosis and sarcopenia · 2022Review
- RNA-based scaffolds for bone regeneration: application and mechanisms of mRNA, miRNA and siRNA.Theranostics · 2020Review
- Applications of RNA interference in the treatment of arthritis.Translational research : the journal of laboratory and clinical medicine · 2019Review
- Does osteogenic potential of clonal human bone marrow mesenchymal stem/stromal cells correlate with their vascular supportive ability?Stem cell research & therapy · 2018Article
- Small non-coding RNAs-based bone regulation and targeting therapeutic strategies.Molecular and cellular endocrinology · 2017Review
- Article
- Hypoxia-inducible factor 1-alpha does not regulate osteoclastogenesis but enhances bone resorption activity via prolyl-4-hydroxylase 2.The Journal of pathology · 2017Article
- Simulation of ECM with Silk and Chitosan Nanocomposite Materials.Journal of materials chemistry. B · 2017Article
- Surface-mediated delivery of siRNA from fibrin hydrogels for knockdown of the BMP-2 binding antagonist noggin.Acta biomaterialia · 2015Article
- Gene therapy for bone engineering.Frontiers in bioengineering and biotechnology · 2015Review
- Characterization of dielectrophoresis-aligned nanofibrous silk fibroin-chitosan scaffold and its interactions with endothelial cells for tissue engineering applications.Acta biomaterialia · 2014Article
- The hypoxia-inducible factor pathway, prolyl hydroxylase domain protein inhibitors, and their roles in bone repair and regeneration.BioMed research international · 2014Review
- Editorial: our enthusiasm for "related research".Clinical orthopaedics and related research · 2013Article
- Developing siRNA therapies to address osteoporosis.Therapeutic delivery · 2013Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOur 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.
methodssiRNAs 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.
resultssiGNAS1 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 10 μg/mL and Day 4 for 100 μg/mL. In vivo, by Day 70, mean bone volume increased compared to Day 7 for siGNAS1-SFCS (47.8 versus 1.8 mg/mL) and siPHD2-SFCS (61.3 versus 1.5 mg/mL).
conclusionsBoth siPHD2 and siGNAS1 support bone regeneration in vivo, whereas only siGNAS1 regulates bone phenotype in MSCs in vitro.
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