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Inhibiting PHD2 in human periodontal ligament cells via lentiviral vector‐mediated RNA interference facilitates cell osteogenic differentiation and periodontal repair

Periodontal defect regeneration in severe periodontitis remains a challenging task in clinic owing to poor survival of seed cells caused by the remaining oxidative stress microenvironment. Recently, the reduction of prolyl hydroxylase domain‐containing protein 2 (PHD2), a primary cellular oxygen sensor, has shown an incredible extensive effect on skeletal muscle tissue regeneration by improving cell resistance to reactive oxygen species, whereas its role in periodontal defect repair is unclear. Here, through lentivirus vector‐mediated RNA interference, the PHD2 gene in human periodontal ligament cells (hPDLCs) is silenced, leading to hypoxia‐inducible factor‐1α stabilization in normoxia. In vitro, PHD2 silencing not only exhibited a satisfactory effect on cell proliferation, but also induced distinguished osteogenic differentiation of hPDLCs. Real‐time polymerase chain reaction and Western blotting revealed significant up‐regulation of osteocalcin, alkaline phosphatase (ALP), runt‐related transcription factor 2, and collagen type I (COL I). Under oxidative stress conditions, COL I and ALP expression levels, suppressed by 100 μM H2O2, were elevated by PHD2‐gene‐silencing in hPDLCs. In vivo, periodontal fenestration defects were established in 18 female Sprague‐Dawley rats aged 6 wk old, followed by implantation of PHD2 silencing hPDLCs in situ for 21 d. Persistent and stable silencing of PHD2 in hPDLCs promoted better new bone formation according to microcomputed tomography 3D reconstruction and related bone parameter analysis. This work demonstrates the therapeutic efficiency of PHD2 gene interference in osteogenic differentiation and periodontal defect repair for highly efficient periodontal regeneration.