The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Adult Human Mesenchymal Stem Cell Differentiation to the Osteogenic or Adipogenic Lineage Is Regulated by Mitogen-activated Protein Kinase
Open accessAbstract
Adult human mesenchymal stem cells are primary, multipotent cells capable of differentiating to osteocytic, chondrocytic, and adipocytic lineages when stimulated under appropriate conditions. To characterize the molecular mechanisms that regulate osteogenic differentiation, we examined the contribution of mitogen-activated protein kinase family members, ERK, JNK, and p38. Treatment of these stem cells with osteogenic supplements resulted in a sustained phase of ERK activation from day 7 to day 11 that coincided with differentiation, before decreasing to basal levels. Activation of JNK occurred much later (day 13 to day 17) in the osteogenic differentiation process. This JNK activation was associated with extracellular matrix synthesis and increased calcium deposition, the two hallmarks of bone formation. Inhibition of ERK activation by PD98059, a specific inhibitor of the ERK signaling pathway, blocked the osteogenic differentiation in a dose-dependent manner, as did transfection with a dominant negative form of MAP kinase kinase (MEK-1). Significantly, the blockage of osteogenic differentiation resulted in the adipogenic differentiation of the stem cells and the expression of adipose-specific mRNAs peroxisome proliferator-activated receptor gamma2, aP2, and lipoprotein lipase. These observations provide a potential mechanism involving MAP kinase activation in osteogenic differentiation of adult stem cells and suggest that commitment of hMSCs into osteogenic or adipogenic lineages is governed by activation or inhibition of ERK, respectively.
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Cited by
Geometric cues for directing the differentiation of mesenchymal stem cells
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Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis
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Biological functions of mesenchymal stem cells and clinical implications
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The Potential of Adipose Stem Cells in Regenerative Medicine
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Metadata
- Authors
- Jaiswal, R. K., Jaiswal, N., Bruder, S. P., Mbalaviele, G., Marshak, D. R., & Pittenger, M. F.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-03
- Volume
- 275
- Issue
- 13
- Pages
- 9645-9652
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2070466054
- Cited by
- 771
- References
- 53
- FWCI
- 9.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Jaiswal, R. K., Jaiswal, N., Bruder, S. P., Mbalaviele, G., Marshak, D. R., & Pittenger, M. F. (2000). Adult Human Mesenchymal Stem Cell Differentiation to the Osteogenic or Adipogenic Lineage Is Regulated by Mitogen-activated Protein Kinase. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.275.13.9645
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