Fluid shear force and hydrostatic pressure jointly promote osteogenic differentiation of BMSCs by activating YAP1 and NFAT2

• Published in: Biotechnology journal 2024-04, Vol.19 (4), p.e2300714-n/a
• Main Authors: Zhou, Yi, Guo, Pan, Jin, Ziyang, Chai, Miaomiao, Zhang, Shuhong, Wang, Xianwei, Tan, Wen‐Song, Zhou, Yan
• Format: Article
• Language: English
• Subjects: Bone Marrow Cells; Cell Differentiation - physiology; Cells, Cultured; Hydrostatic Pressure; Mesenchymal Stem Cells; MSCs; multiple mechanical stimuli; NFAT2; Osteogenesis - physiology; osteogenic differentiation; Transcription Factors - metabolism; YAP1
• ISSN: 1860-6768; 1860-7314
• DOI: 10.1002/biot.202300714

Natural bone tissue features a complex mechanical environment, with cells responding to diverse mechanical stimuli, including fluid shear stress (FSS) and hydrostatic pressure (HP). However, current in vitro experiments commonly employ a singular mechanical stimulus to simulate the mechanical environment in vivo. The understanding of the combined effects and mechanisms of multiple mechanical stimuli remains limited. Hence, this study constructed a mechanical stimulation device capable of simultaneously applying FSS and HP to cells. This study investigated the impact of FSS and HP on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and examined the distinctions and interactions between the two mechanisms. The results demonstrated that both FSS and HP individually enhanced the osteogenic differentiation of BMSCs, with a more pronounced effect observed through their combined application. BMSCs responded to external FSS and HP stimulation through the integrin‐cytoskeleton and Piezo1 ion channel respectively. This led to the activation of downstream biochemical signals, resulting in the dephosphorylation and nuclear translocation of the intracellular transcription factors Yes Associated Protein 1 (YAP1) and nuclear factor of activated T cells 2 (NFAT2). Activated YAP1 could bind to NFAT2 to enhance transcriptional activity, thereby promoting osteogenic differentiation of BMSCs more effectively. This study highlights the significance of composite mechanical stimulation in BMSCs' osteogenic differentiation, offering guidance for establishing a complex mechanical environment for in vitro functional bone tissue construction. Graphical and Lay Summary Bone marrow mesenchymal stem cells (BMSCs) respond to external fluid shear stress (FSS) and hydrostatic pressure (HP) stimuli via the integrin‐cytoskeleton and Piezo1 ion channels, respectively. This activation leads to downstream signaling involving transcription factors YAP1 and NFAT2. The activated YAP1 and NFAT2 proteins exhibit binding capabilities, potentially synergistically enhancing the osteogenic differentiation of BMSCs. This research contributes to a deeper comprehension of the crosstalk relationship between mechanical stimuli in cellular responses.