Promyelocytic leukemia zinc finger mediates glucocorticoid-induced cell cycle arrest in the chondroprogenitor cell line ATDC5

作者：Naito Masako^*; Vongsa Souksavanh; Tsukune Naoya; Ohashi Akiko; Takahashi Tomihisa

来源：Molecular and Cellular Endocrinology, 2015, 417(C): 114-123.

DOI：10.1016/j.mce.2015.09.026

• Glucocorticoid
• Chondrocyte differentiation
• Cell cycle
• PLZF
• CDK inhibitor

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.

• 出版日期2015-12-5