Fluid shear stress and endothelial cells synergistically promote osteogenesis of mesenchymal stem cells via integrin β1-FAK-ERK1/2 pathway.
Mingli JiangQihua ShenYi ZhouWenxia RenMiaomiao ChaiYan ZhouWen-Song TanPublished in: Turkish journal of biology = Turk biyoloji dergisi (2021)
Prevascularization and mechanical stimulation have been reported as effective methods for the construction of functional bone tissue. However, their combined effects on osteogenic differentiation and its mechanism remain to be explored. Here, the effects of fluid shear stress (FSS) on osteogenic differentiation of rat bone-marrow-derived mesenchymal stem cells (BMSCs) when cocultured with human umbilical vein endothelial cells (HUVECs) were investigated, and underlying signaling mechanisms were further explored. FSS stimulation for 1-4 h/day increased alkaline phosphatase (ALP) activity and calcium deposition in coculture systems and promoted the proliferation of cocultured cells. FSS stimulation for 2 h/day was selected as the optimized protocol according to osteogenesis in the coculture. In this situation, the mRNA levels of ALP , runt-related transcriptional factor 2 ( Runx2 ) and osteocalcin ( OCN ), and protein levels of OCN and osteopontin (OPN) in BMSCs were upregulated. Furthermore, FSS and coculture with HUVECs synergistically increased integrin β1 expression in BMSCs and further activated focal adhesion kinases (FAKs) and downstream extracellular signal-related kinase (ERK), leading to the enhancement of Runx2 expression. Blocking the phosphorylation of FAK abrogated FSS-induced ERK phosphorylation and inhibited osteogenesis of cocultured BMSCs. These results revealed that FSS and coculture with HUVECs synergistically promotes the osteogenesis of BMSCs, which was mediated by the integrin β1-FAK-ERK signaling pathway.
Keyphrases
- signaling pathway
- induced apoptosis
- mesenchymal stem cells
- cell migration
- pi k akt
- endothelial cells
- bone marrow
- transcription factor
- high glucose
- cell cycle arrest
- bone regeneration
- poor prognosis
- epithelial mesenchymal transition
- protein kinase
- cell proliferation
- binding protein
- umbilical cord
- cell adhesion
- oxidative stress
- randomized controlled trial
- gene expression
- bone mineral density
- drug induced
- diabetic rats
- small molecule
- cell therapy
- stem cells
- postmenopausal women
- high resolution
- endoplasmic reticulum stress
- biofilm formation
- atomic force microscopy
- staphylococcus aureus
- stress induced
- bone loss