How is mechanobiology involved in mesenchymal stem cell differentiation toward the osteoblastic or adipogenic fate?. Issue 8 (11th January 2019)

• Record Type: Journal Article
• Authors: Benayahu, Dafna; Wiesenfeld, Yarden; Sapir‐Koren, Rony
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 8(2019:Aug.)
• Page Start: 12133
• Page End: 12141
• Publication Date: 2019-01-11
• Subjects: cell niche -- ECM -- mesenchymal cells -- stiffness; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.28099
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: Mechanobiology plays a major role in transducing physical cues from the dynamic cellular environment into biochemical modifications that promote cell‐specific differentiation paths. Mesenchymal stem cells in the bone marrow or in other mesenchymal tissues will differentiate according to the expression of transcription factors (TFs) that govern their lineage commitment. The favoring of either osteogenic or adipogenic differentiation relies on TF expression as well as mechanical properties of the cells' niche that are translated into the activation of certain signaling pathways. Physical factors can induce significant shifts in bipotential lineage commitment between osteogenesis and adipogenesis. The stiffness of the extracellular matrix (ECM) surrounding a cell, varying greatly from rigid environments close to the bone surface to softer regions in the bone marrow, can influence the path of differentiation. Additionally, mechanical loading through exercise appears to favor osteogenesis whereas disuse conditions seem to promote adipogenesis. Abstract : Biomechanical stimuli regulate the bipotential differentiation of mesenchymal cells; loading and high extracellular stiffness lead to osteoblastogenesis whereas unloading and low extracellular stiffness lead to adipogenesis. The Wnt pathway and its interaction with the Yes‐associated protein (YAP)/transcriptional coactivator with PDZ‐binding motif (TAZ) complex acts as a rheostat for reading niche cues that direct mesenchymal stem cell fate. The interplay between activation of Wnt‐β/catenin signaling and YAP/TAZ cytoplasmic or nuclear translocation leads to the transcriptional regulation of these cell lineages.