Zfp521 Is a Target Gene and Key Effector of Parathyroid Hormone-Related Peptide Signaling in Growth Plate Chondrocytes

被引：97

作者：

Correa, Diego ^{[1
]}

Hesse, Eric ^{[1
]}

Seriwatanachai, Dutmanee ^{[2
]}

Kiviranta, Riku ^{[1
]}

Saito, Hiroaki ^{[1
]}

Yamana, Kei ^{[1
,3
]}

Neff, Lynn ^{[1
]}

Atfi, Azeddine ^{[1
]}

Coillard, Lucie ^{[1
]}

Sitara, Despina ^{[2
]}

Maeda, Yukiko ^{[2
]}

Warming, Soren ^{[4
]}

Jenkins, Nancy A. ^{[5
]}

Copeland, Neal G. ^{[5
]}

Horne, William C. ^{[1
]}

Lanske, Beate ^{[2
]}

Baron, Roland ^{[1
,6
]}

机构：

[1] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA

[2] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA

[3] Teijin Pharma Ltd, Teijin Inst Biomed Res, Tokyo 1918512, Japan

[4] Genentech Inc, Mol Biol, San Francisco, CA 94080 USA

[5] Inst Mol & Cell Biol, Canc Genet Lab, Singapore 138673, Singapore

[6] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA

来源：

DEVELOPMENTAL CELL | 2010年 / 19卷 / 04期

基金：

美国国家卫生研究院; 芬兰科学院;

关键词：

INDIAN HEDGEHOG; RETROVIRAL INTEGRATION; HISTONE DEACETYLASES; RUNX2; EXPRESSION; TGF-BETA; IN-VITRO; PTHRP; DIFFERENTIATION; CBFA1; HYPERTROPHY;

D O I：

10.1016/j.devcel.2010.09.008

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

In the growth plate, the interplay between parathyroid hormone-related peptide (PTHrP) and Indian hedgehog (Ihh) signaling tightly regulates chondrocyte proliferation and differentiation during longitudinal bone growth. We found that PTHrP increases the expression of Zfp521, a zinc finger transcriptional coregulator, in prehypertrophic chondrocytes. Mice with chondrocyte-targeted deletion of Zfp521 resembled PTHrP(-/-) and chondrocyte-specific PTHR1(-/-) mice, with decreased chondrocyte proliferation, early hypertrophic transition, and reduced growth plate thickness. Deleting Zfp521 increased expression of Runx2 and Runx2 target genes, and decreased Cyclin D1 and BcI-2 expression while increasing Caspase-3 activation and apoptosis. Zfp521 associated with Runx2 in chondrocytes, antagonizing its activity via an HDAC4-dependent mechanism. PTHrP failed to upregulate Cyclin D1 and to antagonize Runx2, Ihh, and collagen X expression when Zfp521 was absent. Thus, Zfp521 is an important PTHrP target gene that regulates growth plate chondrocyte proliferation and differentiation.

引用

页码：533 / 546

页数：14

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