Effects of dynamic tensile loading on TGF and BMP signaling pathways in mesenchymal stem cells on aligned nanofibrous scaffolds

摘要

Mechanical cues are crucial factors in regulating cellular functions such as proliferation and differentiation. However, it is unclear how external mechanical cues are transduced to the cell nucleus. In this study, we investigated how applied dynamic tensile loading (DL) influences both cell signaling through differentiation pathways and sub-cellular changes in the nucleus of mesenchymal stem cells. DL without exogenous growth factors resulted in a reorganized Lamin A/C (LMAC) network and induced heterochromatin formation and increased fibro-chodrongenic gene expression. Blockade of TGF signaling with SB431542 in DL conditions decreased TGFβ and aggrecan gene expression, and increased BMP2 gene expression. The opposite was observed with the BMP inhibitor LDN193198. However, neither inhibitor blocked LAMC network reorganization and heterochromatin condensation.