Stem Cell and Cancer Biology Group, Indian Institute of Technology Guwahati, Guwahati, Assam, India.
J Biomed Sci. 2013 Sep 26;20(1):71. doi: 10.1186/1423-0127-20-71.
Mesenchymal Stem Cells (MSC) are important candidates for therapeutic applications due to their ex vivo proliferation and differentiation capacity. MSC differentiation is controlled by both intrinsic and extrinsic factors and actin cytoskeleton plays a major role in the event. In the current study, we tried to understand the initial molecular mechanisms and pathways that regulate the differentiation of MSC into osteocytes or adipocytes.
We observed that actin modification was important during differentiation and differentially regulated during adipogenesis and osteogenesis. Initial disruption of actin polymerization reduced further differentiation of MSC into osteocytes and osteogenic differentiation was accompanied by increase in ERK1/2 and p38 MAPK phosphorylation. However, only p38 MAPK phosphorylation was down regulated upon inhibition of actin polymerization which as accompanied by decreased CD49E expression.
Taken together, our results show that actin modification is a pre-requisite for MSC differentiation into osteocytes and adipocytes and osteogenic differentiation is regulated through p38 MAPK phosphorylation. Thus by modifying their cytoskeleton the differentiation potential of MSC could be controlled which might have important implications for tissue repair and regeneration.
间充质干细胞(MSC)由于其体外增殖和分化能力,是治疗应用的重要候选者。MSC 的分化受内在和外在因素的控制,肌动蛋白细胞骨架在该事件中起主要作用。在本研究中,我们试图了解调节 MSC 向成骨细胞或脂肪细胞分化的初始分子机制和途径。
我们观察到,在分化过程中,肌动蛋白修饰很重要,并且在脂肪生成和成骨生成过程中受到不同的调节。肌动蛋白聚合的初始破坏减少了 MSC 进一步分化为成骨细胞,成骨分化伴随着 ERK1/2 和 p38 MAPK 磷酸化的增加。然而,只有在抑制肌动蛋白聚合时,p38 MAPK 磷酸化才被下调,同时 CD49E 表达降低。
综上所述,我们的结果表明,肌动蛋白修饰是 MSC 分化为成骨细胞和脂肪细胞的前提,成骨分化是通过 p38 MAPK 磷酸化来调节的。因此,通过修饰其细胞骨架,可以控制 MSC 的分化潜能,这可能对组织修复和再生具有重要意义。