Zfp521 is a target gene and key effector of parathyroid hormone-related peptide signaling in growth plate chondrocytes.
Zfp521 is a target gene and key effector of parathyroid hormone-related peptide signaling in growth plate chondrocytes.
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DOI：
10.1016/j.devcel.2010.09.008
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发表时间：
2010-10-19
影响因子：
11.8
通讯作者：
Baron, Roland
中科院分区：
文献类型：
--
作者：
Correa, Diego;Hesse, Eric;Seriwatanachai, Dutmanee;Kiviranta, Riku;Saito, Hiroaki;Yamana, Kei;Neff, Lynn;Atfi, Azeddine;Coillard, Lucie;Sitara, Despina;Maeda, Yukiko;Warming, Soren;Jenkins, Nancy A.;Copeland, Neal G.;Horne, William C.;Lanske, Beate;Baron, Roland
在生长板中，甲状旁腺激素相关肽（PTHrP）和印度刺猬（Ihh）信号传导之间的相互作用紧密调节纵向骨生长过程中软骨细胞的增殖和分化。我们发现，PTHrP增加Zfp 521的表达，锌指转录辅助调节，在前肥大软骨细胞。具有Zfp 521的软骨细胞靶向缺失的小鼠类似于PTHrP-/-和软骨细胞特异性PTHR 1-/-小鼠，具有减少的软骨细胞增殖、早期肥大转变和减少的生长板厚度。Zfp 521的缺失增加了Runx 2和Runx 2靶基因的表达，降低了细胞周期蛋白D1和Bcl-2的表达，同时增加了caspase-3的激活和凋亡。Zfp 521与软骨细胞中的Runx 2相关，通过HDAC 4依赖性机制拮抗其活性。当Zfp 521缺失时，PTHrP不能上调cyclin D1的表达，也不能拮抗Runx 2、Ihh和Collagen X的表达。因此，Zfp 521是调节生长板软骨细胞增殖和分化的重要PTHrP靶基因。
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 co-regulator, in pre-hypertrophic 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 Bcl-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 up-regulate 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.
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DOI：
10.1083/jcb.126.6.1611
发表时间：
1994-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Amizuka N;Warshawsky H;Henderson JE;Goltzman D;Karaplis AC
通讯作者：
Karaplis AC
影响因子：
7
作者：
Iwamoto, M;Kitagaki, J;Enomoto-Iwamoto, M
通讯作者：
Enomoto-Iwamoto, M
影响因子：
2.7
作者：
Guo, J;Chung, UI;Kronenberg, HM
通讯作者：
Kronenberg, HM
影响因子：
11.8
作者：
Arnold, Michael A.;Kim, Yuri;Olson, Eric N.
通讯作者：
Olson, Eric N.
影响因子：
15.9
作者：
Chen, L;Adar, R;Deng, CX
通讯作者：
Deng, CX