Effects of hyperglycemia and mechanical stimulations on differentiation fate of mesenchymal stem cells

Increased recruitment of new adipocytes from mesenchymal sources, such as mesenchymal stem cells (MSCs), serves as one of the major causes of excessive adipose tissue formation found in obesity. Both biochemical and biophysical environments surrounding MSCs play key regulatory roles in directing MSC fate decision and terminal differentiation. Of particular interest in relation to diabetes and metabolic disorders is how high glucose levels in hyperglycemia will influence MSC differentiation. Also, how dynamic mechanical loading milieus will affect MSC fate is pivotal considering the effect of exercise on metabolism. In MSC fate decision, literatures have established a mutual antagonistic relationship between osteogenesis and adipogenesis and reported that MSC lineage commitment toward the two fates may rely on a delicate balance between shared signaling pathways and transcription factors. Here we review the data reported on the individual capabilities of hyperglycemia and mechanical loading to control MSC fate into the adipogenic and osteogenic lineages. Additionally, we provide a perspective on the future of the research on how the glucose level and mechanical loading cue may affect MSC fate in a coordinated fashion. Determining optimal extracellular conditions for inhibiting MSC adipogenesis, and better understanding the molecular signaling mechanisms by which it can be achieved, may allow for more effective translational strategies to deal with obesity and related metabolic diseases.