Thymosin Beta-4 Directs Cell Fate Determination of Human Mesenchymal Stem Cells through Biophysical Effects
Thymosin Beta-4 Directs Cell Fate Determination of Human Mesenchymal Stem Cells through Biophysical Effects
复制标题
DOI：
10.1002/jor.20956
复制
发表时间：
2010-01-01
影响因子：
2.8
通讯作者：
Lee, Oscar K.
中科院分区：
文献类型：
--
作者：
Ho, Jennifer H.;Ma, Wei-Hsien;Lee, Oscar K.
细胞分化早期肌动蛋白丝结构的变化指导间充质干细胞（MSCs）的细胞命运定型。胸腺素β-4（T β（4））是一种主要的G-肌动蛋白螯合肽，已知可调节细胞骨架。该研究调查了T β（4）在分化诱导后调节MSC中细胞命运决定的方式。研究发现，T β 4减少了F-actin的形成，降低了F-actin/G-actin的比例，并抑制了成骨分化;这种肌动蛋白重组与早期成骨诱导过程中Runt相关转录因子2基因表达的变化无关。此外，T β（4）反过来促进成脂分化。研究发现，在成脂分化早期，T β（4）处理可上调基因表达并促进脂肪细胞粘附分子的表面表达，这伴随着脂肪细胞表型成熟的加速，但与成脂诱导第一周过氧化物酶体增殖物激活受体γ的差异表达无关。总之，T β（4）通过细胞骨架重组和改变细胞-细胞粘附所产生的生物物理效应而不是直接调节谱系决定转录因子来启动MSC的细胞命运决定。这些发现表明，T β（4），一种普遍存在的肽，当其细胞内浓度升高时，可能与骨质疏松症有关。进一步研究靶向T β（4）用于未来的骨质疏松症治疗是必要的。(C)2009骨科研究学会。由威利期刊公司出版J Orthop Res 28：131-138，2010
Change of actin filament organization at the early stage of cell differentiation directs cell fate commitment of mesenchymal stem cells (MSCs). Thymosin beta-4 (T beta(4)), a major G-actin sequestering peptide, is known to regulate the cytoskeleton. The study investigated the ways in which T beta(4) regulates cell fate determination in MSCs upon differentiation induction. It was found that T beta(4) 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, T beta(4) reciprocally facilitated adipogenic differentiation. T beta(4) 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, T beta(4) 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 T beta(4), a ubiquitous peptide, may be involved in osteoporosis when its intracellular concentration is elevated. Further investigation of targeting T beta(4) for future osteoporosis treatment is warranted. (C) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:131-138, 2010