Sclerostin promotes human dental pulp cells senescence
Background Senescence-related impairment of proliferation and differentiation limits the use of dental pulp cells for tissue regeneration. Deletion of sclerostin improves the dentinogenesis regeneration, while its role in dental pulp senescence is unclear. We investigated the role of sclerostin in s...
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doaj-1676fd4e18ab4a349b3e6651568cd3752020-11-25T01:02:12ZengPeerJ Inc.PeerJ2167-83592018-10-016e580810.7717/peerj.5808Sclerostin promotes human dental pulp cells senescenceYanjing OuYi ZhouShanshan LiangYining WangBackground Senescence-related impairment of proliferation and differentiation limits the use of dental pulp cells for tissue regeneration. Deletion of sclerostin improves the dentinogenesis regeneration, while its role in dental pulp senescence is unclear. We investigated the role of sclerostin in subculture-induced senescence of human dental pulp cells (HDPCs) and in the senescence-related decline of proliferation and odontoblastic differentiation. Methods Immunohistochemical staining and qRT-PCR analyses were performed to examine the expression pattern of sclerostin in young (20–30-year-old) and senescent (45–80-year-old) dental pulps. HDPCs were serially subcultured until senescence, and the expression of sclerostin was examined by qRT-PCR analysis. HDPCs with sclerostin overexpression and knockdown were constructed to investigate the role of sclerostin in HDPCs senescence and senescence-related impairment of odontoblastic differentiation potential. Results By immunohistochemistry and qRT-PCR, we found a significantly increased expression level of sclerostin in senescent human dental pulp compared with that of young human dental pulp. Additionally, elevated sclerostin expression was found in subculture-induced senescent HDPCs in vitro. By sclerostin overexpression and knockdown, we found that sclerostin promoted HDPCs senescence-related decline of proliferation and odontoblastic differentiation potential with increased expression of p16, p53 and p21 and downregulation of the Wnt signaling pathway. Discussion The increased expression of sclerostin is responsible for the decline of proliferation and odontoblastic differentiation potential of HDPCs during cellular senescence. Anti-sclerostin treatment may be beneficial for the maintenance of the proliferation and odontoblastic differentiation potentials of HDPCs.https://peerj.com/articles/5808.pdfSclerostinHuman dental pulp cellSenescencep21p16p53 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yanjing Ou Yi Zhou Shanshan Liang Yining Wang |
spellingShingle |
Yanjing Ou Yi Zhou Shanshan Liang Yining Wang Sclerostin promotes human dental pulp cells senescence PeerJ Sclerostin Human dental pulp cell Senescence p21 p16 p53 |
author_facet |
Yanjing Ou Yi Zhou Shanshan Liang Yining Wang |
author_sort |
Yanjing Ou |
title |
Sclerostin promotes human dental pulp cells senescence |
title_short |
Sclerostin promotes human dental pulp cells senescence |
title_full |
Sclerostin promotes human dental pulp cells senescence |
title_fullStr |
Sclerostin promotes human dental pulp cells senescence |
title_full_unstemmed |
Sclerostin promotes human dental pulp cells senescence |
title_sort |
sclerostin promotes human dental pulp cells senescence |
publisher |
PeerJ Inc. |
series |
PeerJ |
issn |
2167-8359 |
publishDate |
2018-10-01 |
description |
Background Senescence-related impairment of proliferation and differentiation limits the use of dental pulp cells for tissue regeneration. Deletion of sclerostin improves the dentinogenesis regeneration, while its role in dental pulp senescence is unclear. We investigated the role of sclerostin in subculture-induced senescence of human dental pulp cells (HDPCs) and in the senescence-related decline of proliferation and odontoblastic differentiation. Methods Immunohistochemical staining and qRT-PCR analyses were performed to examine the expression pattern of sclerostin in young (20–30-year-old) and senescent (45–80-year-old) dental pulps. HDPCs were serially subcultured until senescence, and the expression of sclerostin was examined by qRT-PCR analysis. HDPCs with sclerostin overexpression and knockdown were constructed to investigate the role of sclerostin in HDPCs senescence and senescence-related impairment of odontoblastic differentiation potential. Results By immunohistochemistry and qRT-PCR, we found a significantly increased expression level of sclerostin in senescent human dental pulp compared with that of young human dental pulp. Additionally, elevated sclerostin expression was found in subculture-induced senescent HDPCs in vitro. By sclerostin overexpression and knockdown, we found that sclerostin promoted HDPCs senescence-related decline of proliferation and odontoblastic differentiation potential with increased expression of p16, p53 and p21 and downregulation of the Wnt signaling pathway. Discussion The increased expression of sclerostin is responsible for the decline of proliferation and odontoblastic differentiation potential of HDPCs during cellular senescence. Anti-sclerostin treatment may be beneficial for the maintenance of the proliferation and odontoblastic differentiation potentials of HDPCs. |
topic |
Sclerostin Human dental pulp cell Senescence p21 p16 p53 |
url |
https://peerj.com/articles/5808.pdf |
work_keys_str_mv |
AT yanjingou sclerostinpromoteshumandentalpulpcellssenescence AT yizhou sclerostinpromoteshumandentalpulpcellssenescence AT shanshanliang sclerostinpromoteshumandentalpulpcellssenescence AT yiningwang sclerostinpromoteshumandentalpulpcellssenescence |
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1725206083230760960 |