Source:http://linkedlifedata.com/resource/pubmed/id/19819988
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rdf:type | |
lifeskim:mentions |
umls-concept:C0007589,
umls-concept:C0007634,
umls-concept:C0205263,
umls-concept:C0237477,
umls-concept:C0249197,
umls-concept:C0288472,
umls-concept:C0598086,
umls-concept:C0598388,
umls-concept:C0851285,
umls-concept:C1332737,
umls-concept:C1415887,
umls-concept:C1419040,
umls-concept:C1420433,
umls-concept:C1420626,
umls-concept:C1424666,
umls-concept:C1511938
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pubmed:issue |
11
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pubmed:dateCreated |
2009-10-28
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/BMP4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 4,
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1b protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1944-9917
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pubmed:author |
pubmed-author:ChangCheng AllenCA,
pubmed-author:ChangShun-FuSF,
pubmed-author:ChangTing-KuoTK,
pubmed-author:ChengCheng-KungCK,
pubmed-author:ChiuJeng-JiannJJ,
pubmed-author:LeeDing-YuDY,
pubmed-author:PengHsin-HsinHH,
pubmed-author:YehChiuan-RenCR,
pubmed-author:YehYi-TingYT,
pubmed-author:ZhouJingJ
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pubmed:issnType |
Electronic
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1827-38
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pubmed:meshHeading |
pubmed-meshheading:19819988-3T3 Cells,
pubmed-meshheading:19819988-Animals,
pubmed-meshheading:19819988-Bone Morphogenetic Protein 4,
pubmed-meshheading:19819988-Cell Cycle,
pubmed-meshheading:19819988-Cell Differentiation,
pubmed-meshheading:19819988-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:19819988-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:19819988-Extracellular Matrix,
pubmed-meshheading:19819988-Gene Expression Regulation,
pubmed-meshheading:19819988-Humans,
pubmed-meshheading:19819988-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:19819988-Mice,
pubmed-meshheading:19819988-Models, Biological,
pubmed-meshheading:19819988-Osteoblasts
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pubmed:year |
2009
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pubmed:articleTitle |
BMP-4 induction of arrest and differentiation of osteoblast-like cells via p21 CIP1 and p27 KIP1 regulation.
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pubmed:affiliation |
Division of Medical Engineering Research, National Chiao Tung University, Hsinchu 30010, Taiwan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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