Increased nuclear stiffness via FAK-ERK1/2 signaling is necessary for synthetic mechano-growth factor E peptide-induced tenocyte migration

Abstract

We have previously reported that a synthetic mechano-growth factor (MGF) C-terminal E-domain with 25 amino acids (MGF-C25E) promotes rat tenocyte migration through the FAK-ERK1/2 signaling pathway. However, the role of the nucleus in MGF-C25E-promoted tenocyte migration and the molecular mechanisms involved remain unclear. In this study, we demonstrate that MGF-C25E increases the Young’s modulus of tenocytes through the FAK-ERK1/2 signaling pathway. This increase is not accompanied by an obvious change in the expression of Lamin A/C but is accompanied by significant chromatin condensation, indicating that MGF-C25E-induced chromatin condensation may contribute to the increased nuclear stiffness. Moreover, DNA methylation is observed in MGF-C25E-treated tenocytes. Inhibition of DNA methylation suppresses the elevation in chromatin condensation, in nuclear stiffness, and in tenocyte migration induced by MGF-C25E. The inhibition of the focal adhesion kinase (FAK) or extracellular signal regulated kinase 1/2 (ERK1/2) signals represses MGF-C25E-promoted DNA methylation. It also abolishes chromatin condensation, nuclear stiffness, and cell migration. Taken together, our results suggest that MGF-C25E promotes tenocyte migration by increasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This provides strong evidence for the role of nuclear mechanics in tenocyte migration and new insight into the molecular mechanisms of MGF-promoted tenocyte migration.

TGF-β1 Pretreatment Improves the Function of Mesenchymal Stem Cells in the Wound Bed

“…Range of concentrations for all the inhibitors were determined from literature reviews and MSCs were treated with 10 μM concentration (Jeon et al, 2008; Qureshi et al, 2008; Gharibi et al, 2012; Zhang et al, 2015, 2016). For adhesion studies cells control and pretreated cells were detached and suspended in inhibitor supplemented serum free media for 2 h before seeding on a 96-well plate.…”

The Heterochromatin Landscape in Migrating Cells and the Importance of H3K27me3 for Associated Transcriptome Alterations

“…Previously, we found that migration of mouse melanoma cells is associated with and dependent on global chromatin condensation that includes more than a two-fold increase in the levels of H3K9me3, H3K27me3, and H4K20me1 [ 14 , 15 , 16 ]. More recently, migration-associated global chromatin condensation was reported in primary and transformed T-cells [ 17 ], primary tenocytes [ 18 ], and mesenchymal stem cells [ 19 ]. Reliance of cell migration on chromatin condensation has been reported in various types of cells, including lung cancer cells [ 20 ], embryonic fibroblasts [ 21 ], breast adenocarcinoma cells [ 22 , 23 , 24 ], colorectal cancer cells [ 24 ], prostate cancer cells [ 25 ], glioma cells [ 26 ], chondrosarcoma cells [ 27 ], epidermal cancer stem cells [ 28 ], primary tenocytes [ 18 ], and primary and transformed T-cells [ 17 ].…”

The use of mechano growth factor to prevent cartilage degeneration in knee osteoarthritis

“…MGF injection was reported as a reliable therapeutic method in an in vivo study, where Deng et al injected 28.5-and 57-μg/kg body weight MGF into the bone deflection area of rabbits to promote osteogenesis and demonstrated that high-dose MGF treatment is more effective in bone repair than low-dose treatment. Zhang et al injected MGF into the ankle joints of rats for tendon repair and reported that 1-μg/ml-MGF treatment had a superior result (Zhang, Luo, Chen, et al, 2016;Zhang, Luo, Kuang, Ju, & Song, 2016). In the present study, three different MGF treatment doses (0.1-10 μg/ml) were used for OA cartilage repair.…”