Abstract
Hypoxia-inducible factors (HIFs) play an important role in angiogenesis, and they can activate the expression of several downstream angiogenic factors. HIF-1 is a major transcriptor of HIFs, composed of α and β subunits. Prolyl hydroxylase domain-containing protein 2 (PHD2) is the main catabolic enzyme for HIF-1α, and it can accelerate its degradation under normoxic conditions. PHD2 expression in bone marrow mesenchymal stem cells (BMMSCs) of SD rats was down-regulated under normoxic conditions in this study by utilizing lentiviral vector-mediated RNA interference to promote HIF-1α accumulation, thus enhancing the expression of angiogenic factors. A tissue-engineered compound was constructed using the composite collagen membrane of BMMSCs after PHD2 gene silencing to repair periodontal fenestration defects in SD rats. The results of this study indicated that, after PHD2 gene silencing, the osteogenic differentiation of BMMSCs was enhanced in vitro, the resistance of cells to oxidative stress was also validated in vitro, thereby illustrating the promotion of the repair of artificially constructed periodontal tissue defects in rats. The results of this study provide a reference and guidance for future applications of RNA interference in periodontal tissue engineering and serve as a basis for improving the survival of seed cells in recipient tissues.
Highlights
IntroductionIt is an clinical condition that must be urgently treated as it can lead to periodontal tissue detachment and alveolar bone defects [1, 2]
Periodontitis is one of the most common chronic oral diseases
Results from the Micro-CT 3D reconstruction and the related bone parameter analysis, as well as histological findings, demonstrated that, compared to the tissue-engineered compound in the control groups, the tissue-engineered compound constructed by combining bone marrow mesenchymal stem cells (BMMSCs) after PHD2 gene silencing and Bio-Gide collagen membrane promoted better rat periodontal tissue repair, including neonatal alveolar bone (NB), neonatal cementum (NC) and neonatal periodontal ligament (NP)
Summary
It is an clinical condition that must be urgently treated as it can lead to periodontal tissue detachment and alveolar bone defects [1, 2]. Bone marrow mesenchymal stem cell (BMMSCs) with multi-potent cells can be used, as they differentiate into several tissue and cell types under different conditions, e.g., fat, bone, cartilage, muscle, etc. BMMSCs have inducing effects on hematopoietic stem cells and are considered to be the ideal seed cells for tissue repair in tissue engineering [5]. Based on several in-depth studies on tissue engineering technology, many scholars believe that more seed cells are required for larger and more complicated tissue defect repairs using this technology, and extensive vasculature is needed to provide seed cells with adequate nutrients [6, 7]. Achieving bone regeneration and revascularization for periodontal tissues and creating a suitable environment for the normal growth of hard and soft tissues required for the restoration of normal structure www.impactjournals.com/oncotarget and functions have become critical issues in the field of periodontal tissue engineering
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