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Replicative Senescence of Periodontal Fibroblasts Induces the Changes in Gene Expression Pattern

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Authors
Min, Byung-Moo; Yi, Tac-Ghee; Jun, Ji-Hae; Kim, Moonkyu; Kim, Gwan-Shik; Baek, Jeong-Hwa
Issue Date
2007-03
Publisher
Korean Acadamy of Oral Biology
Citation
International Journal of Oral Biology, 32:35-43
Keywords
replicative senescenceperiodontal ligament fibroblastsgingival fibroblastsp16INK4Aretinoblastomaintegrin
Abstract
Tooth loss in elderly is mainly caused by alveolar bone loss
via severe periodontitis. Although the severity of periodontitis
is known to be affected by age, the aging process or the
genetic changes during the aging of periodontal tissue cells
are not well characterized. In this study, we investigated the
effect of in vitro aging on the change of gene expression
pattern in periodontal fibroblasts. Gingival fibroblasts (GF)
and periodontal ligament fibroblasts (PDL) were obtained
from two young patients and replicative senescence was
induced by sequential subcultivation. When more than 90%
cells were positively stained with senescence-associated β‚-
galactosidase, those cells were regarded as aged cells. In
aged GF and PDL, the level of phosphorylated retinoblastoma
(RB) and p16INK4A protein was significantly decreased and
increased, respectively. However, the protein level of p53
and p21, well known senescence-inducing genes, did not
increase in aged GF and PDL. Although p27Kip1 and p15INK4B,
another cyclin-dependent kinase inhibitors, were reported
to be involved in replicative senescence of human cells, they
were decreased in aged GF and PDL. Because senescent
cells showed flattened and enlarged cell shape and are
known to have increased focal adhesion, we examined the
protein level of several integrins. Aged GF and PDL showed
increased protein level of integrin α2, αv, and β1. When the
gene expression profiles of actively proliferating young cells
and aged cells were compared by cDNA microarray of
3,063 genes and were confirmed by reverse transcriptionpolymerase
chain reaction, 7 genes and 15 genes were
significantly and commonly increased and decreased, respectively, in aged GF and PDL. Among them, included
are the genes that were known to be involved in the
regulation of cell cycle, gene transcription, or integrin
signaling. The change of gene expression pattern in GF and
PDL was minimally similar to that of oral keratinocyte.
These results suggest that p16INK4A/RB might be involved in
replicative senescence of periodontal fibroblasts and the
change of gene expression profile during aging process is cell
type specific.
ISSN
1226-7155
Language
English
URI
http://hdl.handle.net/10371/69599
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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