کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2094138 | 1081991 | 2015 | 9 صفحه PDF | دانلود رایگان |
• Actin polymerization is measured during osteoblast (OB) differentiation in human stromal stem cells (hMSCs)
• Inhibiting expression of actin depolymerization factors enhances the OB differentiation of hMSCs
• Different actin polymerization regulation chemicals: Phalloidin enhances hMSCs proliferation and OB differentiation, while Cytocholasin D inhibites hMSCs OB differentiation.
• Cofilin phosphorylation loop acts a level for actin polymerization, and regulates osteoblast differentiation through LIM kinase and FAK, JNK and p38 pathways
Remodeling of the actin cytoskeleton through actin dynamics is involved in a number of biological processes, but its role in human stromal (skeletal) stem cells (hMSCs) differentiation is poorly understood. In the present study, we demonstrated that stabilizing actin filaments by inhibiting gene expression of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) in hMSCs, enhanced cell viability and differentiation into osteoblastic cells (OB) in vitro, as well as heterotopic bone formation in vivo. Similarly, treating hMSC with Phalloidin, which is known to stabilize polymerized actin filaments, increased hMSCs viability and OB differentiation. Conversely, Cytocholasin D, an inhibitor of actin polymerization, reduced cell viability and inhibited OB differentiation of hMSC. At a molecular level, preventing Cofilin phosphorylation through inhibition of LIM domain kinase 1 (LIMK1) decreased cell viability and impaired OB differentiation of hMSCs. Moreover, depolymerizing actin reduced FAK, p38 and JNK activation during OB differentiation of hMSCs, while polymerizing actin enhanced these signaling pathways. Our results demonstrate that the actin dynamic reassembly and Cofilin phosphorylation loop is involved in the control of hMSC proliferation and osteoblasts differentiation.
Journal: Stem Cell Research - Volume 15, Issue 2, September 2015, Pages 281–289