Pressure-induced mesenchymal stem cell osteogenesis is dependent on intermediate filament remodeling

What is it about?

Bone can adapt its structure to meet the demands of its physical environment, with enhanced loading seen with exercise promoting bone formation. Osteoblasts are cells that form bone but are limited in supply. Therefore, osteoblasts must be produced from a progenitor cell type called the mesenchymal stem cell (MSC). MSCs directly respond to an applied physical loading by turning into an osteoblast, however how these MSCs sense and transduce that physical stimulus in a bone forming response is poorly understood. In this study, we demonstrate that a physical pressure applied cyclically can enhance the differentiation of MSCs into bone forming osteoblasts. Furthermore, upon the application of this stimulus, MSCs disrupt and remodel part of their cytoskeleton call the intermediate filament (IF) network. Moreover, we demonstrate for the first time that this alteration in the IF network is required for pressure induced differentiation of MSCs into osteoblasts leading to subsequent bone formation. Lastly and most importantly, we also demonstrate that this mechanism can be targeted using a drug to mimic the beneficial effect of exercise, demonstrating a potential new therapy for bone loss diseases such as osteoporosis.

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