RRC ID 1351
著者 Nakajima M, Negishi Y, Tanaka H, Kawashima K.
タイトル p21(Cip-1/SDI-1/WAF-1) expression via the mitogen-activated protein kinase signaling pathway in insulin-induced chondrogenic differentiation of ATDC5 cells.
ジャーナル Biochem Biophys Res Commun
Abstract The embryonal carcinoma-derived cell line, ATDC5, differentiates into chondrocytes in response to insulin or insulin-like growth factor-I stimulation. In this study, we investigated the roles of mitogen-activated protein (MAP) kinases in insulin-induced chondrogenic differentiation of ATDC5 cells. Insulin-induced accumulation of glycosaminoglycan and expression of chondrogenic differentiation markers, type II collagen, type X collagen, and aggrecan mRNA were inhibited by the MEK1/2 inhibitor (U0126) and the p38 MAP kinase inhibitor (SB203580). Conversely, the JNK inhibitor (SP600125) enhanced the synthesis of glycosaminoglycan and expression of chondrogenic differentiation markers. Insulin-induced phosphorylation of ERK1/2 and JNK but not that of p38 MAP kinase. We have previously clarified that the induction of the cyclin-dependent kinase inhibitor, p21(Cip-1/SDI-1/WAF-1), is essential for chondrogenic differentiation of ATDC5 cells. To assess the relationship between the induction of p21 and MAP kinase activity, we investigated the effect of these inhibitors on insulin-induced p21 expression in ATDC5 cells. Insulin-induced accumulation of p21 mRNA and protein was inhibited by the addition of U0126 and SB203580. In contrast, SP600125 enhanced it. Inhibitory effects of U0126 or stimulatory effects of SP600125 on insulin-induced chondrogenic differentiation were observed when these inhibitors exist in the early phase of differentiation, suggesting that MEK/ERK and JNK act on early phase differentiation. SB202580, however, is necessary not only for early phase but also for late phase differentiation, indicating that p38 MAP kinase stimulates differentiation by acting during the entire period of cultivation. These results for the first time demonstrate that up-regulation of p21 expression by ERK1/2 and p38 MAP kinase is required for chondrogenesis, and that JNK acts as a suppressor of chondrogenesis by down-regulating p21 expression.
巻・号 320(4)
ページ 1069-75
公開日 2004-8-6
DOI 10.1016/j.bbrc.2004.06.057
PII S0006291X04013427
PMID 15249198
MeSH Animals Anthracenes / pharmacology Butadienes / pharmacology Cell Differentiation / drug effects Cell Differentiation / physiology Cell Line Chondrocytes / drug effects Chondrocytes / metabolism* Chondrogenesis / drug effects Chondrogenesis / physiology* Cyclin-Dependent Kinase Inhibitor p21 Cyclins / metabolism* Imidazoles / pharmacology Insulin / pharmacology* Mice Mitogen-Activated Protein Kinases / antagonists & inhibitors Mitogen-Activated Protein Kinases / metabolism* Nitriles / pharmacology Pyridines / pharmacology Signal Transduction / drug effects Signal Transduction / physiology
IF 2.985
引用数 29
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 ATDC5(RCB0565)