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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

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 a...

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Autores principales: Choi, Yoon Jung, Lee, Jue Yeon, Chung, Chong Pyoung, Park, Yoon Jeong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459692/
https://www.ncbi.nlm.nih.gov/pubmed/23049256
http://dx.doi.org/10.2147/IJN.S31723
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author Choi, Yoon Jung
Lee, Jue Yeon
Chung, Chong Pyoung
Park, Yoon Jeong
author_facet Choi, Yoon Jung
Lee, Jue Yeon
Chung, Chong Pyoung
Park, Yoon Jeong
author_sort Choi, Yoon Jung
collection PubMed
description 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. CONCLUSION: 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.
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spelling pubmed-34596922012-10-03 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 Choi, Yoon Jung Lee, Jue Yeon Chung, Chong Pyoung Park, Yoon Jeong Int J Nanomedicine Original Research 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. CONCLUSION: 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. Dove Medical Press 2012 2012-09-21 /pmc/articles/PMC3459692/ /pubmed/23049256 http://dx.doi.org/10.2147/IJN.S31723 Text en © 2012 Choi et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Original Research
Choi, Yoon Jung
Lee, Jue Yeon
Chung, Chong Pyoung
Park, Yoon Jeong
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
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459692/
https://www.ncbi.nlm.nih.gov/pubmed/23049256
http://dx.doi.org/10.2147/IJN.S31723
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