Sirt6 regulates postnatal growth plate differentiation and proliferation via Ihh signaling

被引：40

作者：

Piao, Jinying ^{[1
]}

Tsuji, Kunikazu ^{[2
]}

Ochi, Hiroki ^{[3
]}

Iwata, Munetaka ^{[4
]}

Koga, Daisuke ^{[5
]}

Okawa, Atsushi ^{[5
]}

Morita, Sadao ^{[1
]}

Takeda, Shu ^{[6
]}

Asou, Yoshinori ^{[5
]}

机构：

[1] Tokyo Med & Dent Univ, Dept Rehabil Med, Grad Sch, Bunkyo Ku, Tokyo 1138519, Japan

[2] Tokyo Med & Dent Univ, Dept Joint Surg & Sports Med, Sect Cartilage Regenerat, Bunkyo Ku, Tokyo 1138519, Japan

[3] Nippon Vet & Life Sci Univ, Lab Vet Microbiol, Tokyo 1808602, Japan

[4] Nippon Vet & Life Sci Univ, Sch Vet Med, Div Vet Surg, Tokyo 1808602, Japan

[5] Tokyo Med & Dent Univ, Dept Orthoped Surg, Bunkyo Ku, Tokyo 1138519, Japan

[6] Tokyo Med & Dent Univ, Dept Physiol & Cell Biol, Bunkyo Ku, Tokyo 1138519, Japan

来源：

SCIENTIFIC REPORTS | 2013年 / 3卷

关键词：

DEPENDENT GENE-EXPRESSION; LONGITUDINAL BONE-GROWTH; INDIAN HEDGEHOG; CARTILAGE; PROTEIN; CHONDROCYTES; CELLS; PTHRP; DEACETYLATION; PURMORPHAMINE;

D O I：

10.1038/srep03022

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

共 46 条

[1] TGFβ and PTHrP control chondrocyte proliferation by activating cyclin D1 expression [J].

Beier, F ;

Ali, Z ;

Mok, D ;

Taylor, AC ;

Leask, T ;

Albanese, C ;

Pestell, RG ;

LuValle, P .

MOLECULAR BIOLOGY OF THE CELL, 2001, 12 (12) :3852-3863

[2] δ-EF1 is a negative regulator of Ihh in the developing growth plate [J].

Bellon, Ellen ;

Luyten, Frank P. ;

Tylzanowski, Przemko .

JOURNAL OF CELL BIOLOGY, 2009, 187 (05) :685-699

[3] The Sir2 family of protein deacetylases [J].

Blander, G ;

Guarente, L .

ANNUAL REVIEW OF BIOCHEMISTRY, 2004, 73 :417-435

[4] SIRT6 protects human endothelial cells from DNA damage, telomere dysfunction, and senescence [J].

Cardus, Anna ;

Uryga, Anna K. ;

Walters, Gareth ;

Erusalimsky, Jorge D. .

CARDIOVASCULAR RESEARCH, 2013, 97 (03) :571-579

[5]

Deckelbaum RA, 2002, J CELL SCI, V115, P3015

[6] Primary culture and phenotyping of murine chondrocytes [J].

Gosset, Marjolaine ;

Berenbaum, Francis ;

Thirion, Sylvie ;

Jacques, Claire .

NATURE PROTOCOLS, 2008, 3 (08) :1253-1260

[7] The world according to Hedgehog [J].

Hammerschmidt, M ;

Brook, A ;

McMahon, AP .

TRENDS IN GENETICS, 1997, 13 (01) :14-21

[8] PHYSIOLOGICAL-MECHANISMS ADOPTED BY CHONDROCYTES IN REGULATING LONGITUDINAL BONE-GROWTH IN RATS [J].

HUNZIKER, EB ;

SCHENK, RK .

JOURNAL OF PHYSIOLOGY-LONDON, 1989, 414 :55-71

[9] QUANTITATION OF CHONDROCYTE PERFORMANCE IN GROWTH-PLATE CARTILAGE DURING LONGITUDINAL BONE-GROWTH [J].

HUNZIKER, EB ;

SCHENK, RK ;

CRUZORIVE, LM .

JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 1987, 69A (02) :162-173

[10] Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase [J].

Imai, S ;

Armstrong, CM ;

Kaeberlein, M ;

Guarente, L .

NATURE, 2000, 403 (6771) :795-800

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