title: Cell-penetrating superoxide dismutase attenuates oxidative stress-induced senescence by regulating the p53-p21(Cip1) pathway and restores osteoblastic differentiation in human dental pulp stem cells.
abstract: BACKGROUND
  Human dental pulp stem cells (DPSCs) have potential applications in tissue regeneration because of their convenient cell harvesting procedures and multipotent capacity. However, the tissue regenerative potential of DPSCs is known to be negatively regulated by aging in long-term culture and under oxidative stress. With an aim of reducing cellular senescence and oxidative stress in DPSCs, an intracellular delivery system for superoxide dismutase 1 (SOD1) was developed. We conjugated SOD1 with a cell-penetrating peptide known as low-molecular weight protamine (LMWP), and investigated the effect of LMWP-SOD1 conjugates on hydrogen peroxide-induced cellular senescence and osteoblastic differentiation.
  
  
  RESULTS
  LMWP-SOD1 significantly attenuated enlarged and flattened cell morphology and increased senescence-associated β-galactosidase activity. Under the same conditions, LMWP-SOD1 abolished activation of the cell cycle regulator proteins, p53 and p21(Cip1), induced by hydrogen peroxide. In addition, LMWP-SOD1 reversed the inhibition of osteoblastic differentiation and downregulation of osteogenic gene markers induced by hydrogen peroxide. However, LMWP-SOD1 could not reverse the decrease in odontogenesis caused by hydrogen peroxide.
  
  
  CONCLUSIONS
  Overall, cell-penetrating LMWP-SOD1 conjugates are effective for attenuation of cellular senescence and reversal of osteoblastic differentiation of DPSCs caused by oxidative stress inhibition. This result suggests potential application in the field of antiaging and tissue engineering to overcome the limitations of senescent stem cells.
authors.affiliation: Craniomaxillofacial Reconstructive Sciences, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: Yoon Jung
authors.initials: YJ
authors.lastname: Choi
authors.forename: Jue Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Chong Pyoung
authors.initials: CP
authors.lastname: Chung
authors.forename: Yoon Jeong
authors.initials: YJ
authors.lastname: Park
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D003782:Dental Pulp / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D013482:Superoxide Dismutase / Q000008:administration & dosage*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; D013482:Superoxide Dismutase