| Effect of phosphatidyl inositol 3-kinase, extracellular signal-regulated kinases 1/2, and p38 mitogen-activated protein kinase inhibition on osteogenic differentiation of muscle-derived stem cells. | |
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MedLine Citation:
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PMID: 20617875 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Skeletal muscle-derived stem cells (MDSCs) can undergo osteogenesis when treated with bone morphogenetic proteins (BMPs), making them a potential cell source for bone tissue engineering. The signaling pathways that regulate BMP4-induced osteogenesis in MDSCs are not well understood, although they may provide a means to better regulate differentiation during bone regeneration. The objective of this study was to characterize the signaling pathways involved in the BMP4-induced osteogenesis of MDSCs. Cells were treated with BMP4 and specific inhibitors to the extracellular signal-regulated kinases 1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and phosphatidyl inositol 3-kinase (PI3K) pathways (PD98059, SB203580, and Ly294002, respectively). Cellular proliferation, expression of osteoblast-related genes, alkaline phosphatase (ALP) activity, and tissue mineralization were measured to determine the role of each pathway in the osteogenic differentiation of MDSCs. Inhibition of the ERK1/2 pathway increased ALP activity and mineralization, whereas inhibition of the p38 MAPK pathway decreased osteogenesis, suggesting opposing roles of these pathways in the BMP4-induced osteogenesis of MDSCs. Inhibition of the PI3K pathway significantly increased mineralization by MDSCs. These findings highlight the involvement of the ERK1/2, p38 MAPK, and PI3K pathways in opposing capacities in MDSC differentiation and warrant further investigation, as it may identify novel therapeutic targets for the development of stem cell-based therapies for bone tissue engineering. |
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Authors:
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Karin A Payne; Laura B Meszaros; Julie A Phillippi; Johnny Huard |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-08-28 |
Journal Detail:
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Title: Tissue engineering. Part A Volume: 16 ISSN: 1937-335X ISO Abbreviation: Tissue Eng Part A Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-14 Completed Date: 2011-04-07 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 101466659 Medline TA: Tissue Eng Part A Country: United States |
Other Details:
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Languages: eng Pagination: 3647-55 Citation Subset: IM |
Affiliation:
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Stem Cell Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bone Morphogenetic Protein 4 / pharmacology Cell Differentiation / drug effects Cell Proliferation / drug effects Cell Survival / drug effects Cells, Cultured Chromones / pharmacology Enzyme Inhibitors / pharmacology Flavonoids / pharmacology Imidazoles / pharmacology Mice Mice, Inbred C57BL Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors, metabolism* Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors, metabolism* Morpholines / pharmacology Muscle Cells / cytology*, drug effects Osteogenesis / drug effects Phosphatidylinositol 3-Kinases / antagonists & inhibitors, metabolism* Pyridines / pharmacology Reverse Transcriptase Polymerase Chain Reaction Stem Cells / cytology*, drug effects p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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1 R01 DE13420-06/DE/NIDCR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Bone Morphogenetic Protein 4; 0/Chromones; 0/Enzyme Inhibitors; 0/Flavonoids; 0/Imidazoles; 0/Morpholines; 0/PD 98059; 0/Pyridines; 0/SB 203580; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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