Thymosin beta‐4 directs cell fate determination of human mesenchymal stem cells through biophysical effects
Open Access
- 27 July 2009
- journal article
- research article
- Published by Wiley in Journal of Orthopaedic Research
- Vol. 28 (1), 131-138
- https://doi.org/10.1002/jor.20956
Abstract
Change of actin filament organization at the early stage of cell differentiation directs cell fate commitment of mesenchymal stem cells (MSCs). Thymosin beta‐4 (Tβ4), a major G‐actin sequestering peptide, is known to regulate the cytoskeleton. The study investigated the ways in which Tβ4 regulates cell fate determination in MSCs upon differentiation induction. It was found that Tβ4 decreased F‐actin formation, reduced the F‐actin/G‐actin ratio, and inhibited osteogenic differentiation; such actin reorganization was not associated with the change of Runt‐related transcription factor 2 gene expression during early osteogenic induction. Besides, Tβ4 reciprocally facilitated adipogenic differentiation. Tβ4 treatment was found to up‐regulate gene as well as promote surface expression of adipocyte adhesion molecule during early adipogenic differentiation, which accompanied acceleration of adipocyte phenotypic maturation but was not associated with differential expression of peroxisome proliferator‐activated receptor gamma during the first week of adipogenic induction. In summary, Tβ4 initiated cell fate determination of MSCs through biophysical effects exerted by cytoskeleton reorganization and altered cell‐cell adhesion rather than direct regulation of lineage‐determining transcriptional factors. Such findings suggest that Tβ4, a ubiquitous peptide, may be involved in osteoporosis when its intracellular concentration is elevated. Further investigation of targeting Tβ4 for future osteoporosis treatment is warranted. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:131–138, 2010Keywords
This publication has 24 references indexed in Scilit:
- Engineering amount of cell–cell contact demonstrates biphasic proliferative regulation through RhoA and the actin cytoskeletonExperimental Cell Research, 2008
- Modulation of Cellular Mechanics during Osteogenic Differentiation of Human Mesenchymal Stem CellsBiophysical Journal, 2007
- Altered Membrane Dynamics of Quantum Dot-Conjugated Integrins during Osteogenic Differentiation of Human Bone Marrow Derived Progenitor CellsBiophysical Journal, 2007
- Changes in integrin expression during adipocyte differentiationCell Metabolism, 2005
- Identification of adipocyte adhesion molecule (ACAM), a novel CTX gene family, implicated in adipocyte maturation and development of obesityBiochemical Journal, 2005
- Thymosin β4increases hair growth by activation of hair follicle stem cellsThe FASEB Journal, 2003
- Multiple Signaling Pathways Converge on the Cbfa1/Runx2 Transcription Factor to Regulate Osteoblast DifferentiationConnective Tissue Research, 2003
- A new mathematical model for relative quantification in real-time RT-PCRNucleic Acids Research, 2001
- Mesenchymal stem cellsJournal of Orthopaedic Research, 1991
- Effects of cytochalasin and phalloidin on actin.The Journal of cell biology, 1987