Browsing by Author "Chang, Cheng Allen"

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BMP-4 Induction of Arrest and Differentiation of Osteoblast-Like Cells via p21(CIP1) and p27(KIP1) Regulation
(2009-11-01)
Chang, Shun-Fu
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Chang, Ting-Kuo
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Peng, Hsin-Hsin
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Yeh, Yi-Ting
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Lee, Ding-Yu
Cell cycle regulation by differentiation signals is critical for eukaryote development. We investigated the roles of bone morphogenetic protein (BMP)-4, an important stimulator of osteoblast differentiation and bone formation, in regulating cell cycle distribution in four osteoblast-like cell lines and mouse primary osteoblasts, and the underlying mechanisms. In all cells used, BMP-4 induced G(0)/G(1) arrest. The molecular basis of the BMP-4 effect was analyzed, and the presentation on molecular mechanism is focused on human MG63 cells. BMP-4 induced p21(CIP1) and p27(KIP1) expressions and hence cell differentiation but had no effects on the expressions of cyclins A, B1, D1, and E, cyclin-dependent protein kinase-2, -4, and -6. Using specific small interfering RNA (siRNA), we found that BMP-4-induced G(0)/G(1) arrest, and p21(CIP1) and p27(KIP1) expressions were mediated by BMP receptor type IA (BMPRIA)-specific Sma- and Mad-related protein (Smad)1/5. BMP-4 induced transient phosphorylations of ERK; transfection of MG63 cells with ERK2, but not ERK1, -specific siRNA inhibited the BMP-4-induced responses in MG63 cells. Pretreatment of MG63 cells with Arg-Gly-Asp-Ser, which blocks the cell-extracellular matrix interaction, or transfection with beta(3) integrin-specific siRNA inhibited BMP-4-induced ERK and Smad1/5 phosphorylations. BMP-4 induced transient increases in associations of beta(3)-integrin with focal adhesion kinase and Shc, the dominant-negative mutants of which inhibited BMP-4-induced ERK and Smad1/5 phosphorylations. Our results indicate that BMP-4 induces G(0)/G(1) arrest and hence differentiation in osteoblast-like cells through increased expressions of p21(CIP1) and p27(KIP1), which are mediated by BMPRIA-specific Smad1/5. The extracellular matrix/beta(3) integrin/focal adhesion kinase/Shc/ERK2 signaling pathway is involved in these BMP-4-induced responses in osteoblast-like cells. (Molecular Endocrinology 23: 1827-1838, 2009)
Mechanical Force Induces G2/M Cell Cycle Arrest in Human Osteosarcoma Cells and Inhibits Their Differentiation
(2008-04-01)
Chang, Shun-Fu
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Chang, Cheng Allen
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Chiu, Jeng-Jiann
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Chien, Shu
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交大名義發表
Tumor cell cycle arrest induced by shear stress: Roles of integrins and Smad
(2008-03-11)
Chang, Shun-Fu
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Chang, Cheng Allen
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Lee, Ding-Yu
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Leet, Pei-Ling
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Yeh, Yu-Ming
interstitial flow in and around tumor tissue affects the mechanical microenvironment to modulate tumor cell growth and metastasis. We investigated the roles of flow-induced shear stress in modulating cell cycle distribution in four tumor cell lines and the underlying mechanisms. In all four cell lines, incubation under static conditions for 24 or 48 h led to G(0)/G(1) arrest; in contrast, shear stress (12 dyneS/cm(2)) induced G(2)/M arrest. The molecular basis of the shear effect was analyzed, and the presentation on molecular mechanism is focused on human MG63 osteosarcoma cells. Shear stress induced increased expressions of cyclin 11311 and p21(CIP1) and decreased expressions of cyclins A, D1, and E, cyclin-dependent protein kinases (Cdk)-1, -2, -4, and -6, and p27(KIP1) as well as a decrease in Cdk1 activity. Using specific antibodies and small interfering RNA, we found that the shear-induced G2/M arrest and corresponding changes in G2/M regulatory protein expression and activity were mediated by alpha(v)beta(3) and beta(1), integrins through bone morphogenetic protein receptor type IA-specific Smad1 and Smad5. Shear stress also down-regulated runt-related transcription factor 2 (Runx2) binding activity and osteocalcin and alkaline phosphatase expressions in MG63 cells; these responses were mediated by alpha(v)beta(3) and beta(1), integrins through Smad5. Our findings provide insights into the mechanism by which shear stress induces G(2)/M arrest in tumor cells and inhibits cell differentiation and demonstrate the importance of mechanical microenvironment in modulating molecular signaling, gene expression, cell cycle, and functions in tumor cells.
Use of statistical methods to find the polysaccharide structural characteristics and the relationships between monosaccharide composition ratio and macrophage stimulatory activity of regionally different strains of Lentinula edodes
(2007-02-12)
Lo, Tiffany Chien Ting
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Jiang, Yi Huei
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Chao, Anne Lien Ju
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Chang, Cheng Allen
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生物科技學系
Multiple linear regression analysis was used to deduce the correlation between the monosaccharide composition ratios of 10 regionally different strains of Lentinula edodes and their in vitro macrophage stimulatory activities. Arabinose, xylose, mannose and galactose were identified as the monosaccharides that could be related to macrophage stimulatory activities. Additional principal component analysis and factor analysis methods were used to treat the same monosaccharide composition ratio data and the compositions of arabinose, xylose, mannose and galactose were found to be important. Interestingly, glucose, although presented in large compositions in all strains presumably forms the backbone of the polysaccharide structures, is not selected as the determinant factor for either structural characteristics or that of the in vitro macrophage stimulatory activities. (c) 2006 Elsevier B.V. All rights reserved.