RRC ID |
62024
|
著者 |
Piao J, Tsuji K, Ochi H, Iwata M, Koga D, Okawa A, Morita S, Takeda S, Asou Y.
|
タイトル |
Sirt6 regulates postnatal growth plate differentiation and proliferation via Ihh signaling.
|
ジャーナル |
Sci Rep
|
Abstract |
Sirtuin 6 (Sirt6) is a mammalian homologue of NAD⁺-dependent histone deacetylase Sir2. Although Sirt6⁻/⁻ mice exhibit growth retardation, the role of Sirt6 in cartilage metabolism is unclear. The aim of this study was to investigate the Sirt6 signaling pathway in cartilage metabolism. Immunohistological evaluation of the tibial growth plate in Sirt6⁻/⁻ mice exhibited impaired proliferation and differentiation of chondrocytes, reduced expression of Indian hedgehog (Ihh), and a senescent phenotype. When Sirt6 was knocked down in chondrocytes in vitro, expression of Ihh and its downstream genes were reduced. Impaired differentiation by Sirt6 silencing was completely rescued by administration of a Hh signal agonist. When sirtuins were activated, chondrocyte differentiation was enhanced together with activation of Ihh signal, and these effects were abrogated by Sirt6 silencing. ChIP assay revealed the affinity of ATF4 to the Ihh promoter was markedly decreased by Sirt6 knockdown. These data indicate Sirt6 directly controls proliferation and differentiation of chondrocytes.
|
巻・号 |
3
|
ページ |
3022
|
公開日 |
2013-10-23
|
DOI |
10.1038/srep03022
|
PII |
srep03022
|
PMID |
24149372
|
PMC |
PMC6505680
|
MeSH |
Activating Transcription Factor 4 / metabolism
Animals
Cell Differentiation / genetics
Cell Line
Cell Proliferation
Chondrocytes / cytology
Chondrocytes / metabolism
Dwarfism / genetics
Gene Expression Regulation
Genotype
Growth Plate / growth & development*
Growth Plate / metabolism*
Growth Plate / pathology
Hedgehog Proteins / metabolism*
Mice
Mice, Knockout
Promoter Regions, Genetic
Protein Binding
Signal Transduction*
Sirtuins / genetics*
Sirtuins / metabolism*
|
IF |
3.998
|
リソース情報 |
ヒト・動物細胞 |
ATDC5(RCB0565) |