早幼粒细胞白血病锌指蛋白介导糖皮质激素诱导的软骨祖细胞系ATDC5细胞周期停滞。
Promyelocytic leukemia zinc finger mediates glucocorticoid-induced cell cycle arrest in the chondroprogenitor cell line ATDC5.
作者信息
Naito Masako, Vongsa Souksavanh, Tsukune Naoya, Ohashi Akiko, Takahashi Tomihisa
机构信息
Department of Anatomy, Nihon University School of Dentistry, Tokyo, Japan; Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan.
Department of Anatomy, Nihon University School of Dentistry, Tokyo, Japan; Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan.
出版信息
Mol Cell Endocrinol. 2015 Dec 5;417:114-23. doi: 10.1016/j.mce.2015.09.026. Epub 2015 Sep 28.
Glucocorticoids (GCs) affect the proliferation of growth plate chondrocytes. In this study, we investigated the role of the GC-inducible promyelocytic leukemia zinc finger (PLZF) gene in chondrocyte differentiation by using the chondrogenic cell line ATDC5. PLZF overexpression suppressed cell cycle progression (p < 0.01) and promoted differentiation into hypertrophic chondrocytes by inducing mRNA expression of alkaline phosphatase (p < 0.01), and the cyclin-dependent kinase (CDK) inhibitor p21 (p < 0.01). In contrast, PLZF knockdown impaired differentiation into hypertrophic chondrocytes and promoted cell cycle progression (p < 0.01). Treatment with the GC analogue dexamethasone (10(-6) M) suppressed cell cycle progression in ATDC5 cells. PLZF shRNA attenuated dexamethasone-induced cell cycle arrest (p < 0.01) by downregulating the mRNA expression of the CDK inhibitors p21 and p57 (p < 0.01). These results clearly indicated that PLZF promoted differentiation into hypertrophic chondrocytes and mediated dexamethasone-induced cell cycle arrest by regulating CDK inhibitors.
糖皮质激素（GCs）影响生长板软骨细胞的增殖。在本研究中，我们通过使用软骨形成细胞系ATDC5，研究了GC诱导的早幼粒细胞白血病锌指（PLZF）基因在软骨细胞分化中的作用。PLZF过表达抑制细胞周期进程（p < 0.01），并通过诱导碱性磷酸酶的mRNA表达（p < 0.01）和细胞周期蛋白依赖性激酶（CDK）抑制剂p21（p < 0.01）促进向肥大软骨细胞的分化。相反，PLZF敲低损害向肥大软骨细胞的分化并促进细胞周期进程（p < 0.01）。用GC类似物地塞米松（10(-6) M）处理可抑制ATDC5细胞的细胞周期进程。PLZF shRNA通过下调CDK抑制剂p21和p57的mRNA表达（p < 0.01）减弱地塞米松诱导的细胞周期停滞（p < 0.01）。这些结果清楚地表明，PLZF通过调节CDK抑制剂促进向肥大软骨细胞的分化并介导地塞米松诱导的细胞周期停滞。
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