title: Promyelocytic leukemia zinc finger mediates glucocorticoid-induced cell cycle arrest in the chondroprogenitor cell line ATDC5.
abstract: 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.
authors.affiliation: Department of Anatomy, Nihon University School of Dentistry, Tokyo, Japan; Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan. Electronic address: naitou.masako@nihon-u.ac.jp.
authors.forename: Masako
authors.initials: M
authors.lastname: Naito
authors.affiliation: Department of Anatomy, Nihon University School of Dentistry, Tokyo, Japan; Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: Souksavanh
authors.initials: S
authors.lastname: Vongsa
authors.affiliation: Department of Periodontology, Nihon University School of Dentistry, Tokyo, Japan; Division of Advanced Dental Treatment, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Tsukune
authors.affiliation: Department of Anatomy, Nihon University School of Dentistry, Tokyo, Japan; Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Ohashi
authors.affiliation: Department of Anatomy, Nihon University School of Dentistry, Tokyo, Japan; Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: Tomihisa
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D000075722:Promyelocytic Leukemia Zinc Finger Protein
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005938:Glucocorticoids; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C513267:Zbtb16 protein, mouse; D003907:Dexamethasone; D000469:Alkaline Phosphatase
keywords: CDK inhibitor; Cell cycle; Chondrocyte differentiation; Glucocorticoid; PLZF