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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

Payne, KA and Meszaros, LB and Phillippi, JA and Huard, J (2010) 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. Tissue Engineering - Part A, 16 (12). 3647 - 3655. ISSN 1937-3341

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Abstract

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. © 2010 Mary Ann Liebert, Inc.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Payne, KA
Meszaros, LB
Phillippi, JA
Huard, J
Centers: Other Centers, Institutes, or Units > Stem Cell Research Center
Date: 1 December 2010
Date Type: Publication
Journal or Publication Title: Tissue Engineering - Part A
Volume: 16
Number: 12
Page Range: 3647 - 3655
DOI or Unique Handle: 10.1089/ten.tea.2009.0738
Schools and Programs: School of Medicine > Biochemistry and Molecular Genetics
School of Medicine > Orthopaedic Surgery
School of Medicine > Surgery
Swanson School of Engineering > Bioengineering
Refereed: Yes
ISSN: 1937-3341
MeSH Headings: 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; Mitogen-Activated Protein Kinase 1--metabolism; Mitogen-Activated Protein Kinase 3--antagonists & inhibitors; Mitogen-Activated Protein Kinase 3--metabolism; Morpholines--pharmacology; Muscle Cells--cytology; Muscle Cells--drug effects; Osteogenesis--drug effects; Phosphatidylinositol 3-Kinases--antagonists & inhibitors; Phosphatidylinositol 3-Kinases--metabolism; Pyridines--pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Stem Cells--cytology; Stem Cells--drug effects; p38 Mitogen-Activated Protein Kinases--antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases--metabolism
Other ID: NLM PMC2991210
PubMed Central ID: PMC2991210
PubMed ID: 20617875
Date Deposited: 04 Apr 2014 16:47
Last Modified: 02 Feb 2019 16:58
URI: http://d-scholarship.pitt.edu/id/eprint/20940

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