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)