Nuclear mechanosensing controls MSC osteogenic potential through HDAC epigenetic remodeling

• DOI: 10.1073/pnas.2006765117
• Publication Date: 2020-08-18T00:36:13Z
• Authors: Anouk R. Killaars; Cierra J. Walker; Kristi S. Anseth
• Keywords: Cell Nucleus; 0301 basic medicine; Acetylation; Cell Differentiation; Hydrogels; Mesenchymal Stem Cells; Biological Sciences; Hydroxamic Acids; Histone Deacetylases; Epigenesis, Genetic; Extracellular Matrix; Histone Deacetylase Inhibitors; Histones; 03 medical and health sciences; Osteogenesis; Humans; Mechanoreceptors; Cells, Cultured

Significance The extracellular matrix is highly dynamic and presents mechanical signals to the residing cells to maintain tissue homeostasis. Recently, the nucleus has been implicated to be a direct mechanosensor, and dysregulation of nuclear mechanosensing might be involved in several diseases, including bone degeneration. To better understand mechanisms behind remodeling of the epigenetic landscape through nuclear mechanosensing, we utilize an innovative photostiffening hydrogel platform to manipulate nuclear mechanosensing in human mesenchymal stem cells. Our results reveal that disruption of nuclear mechanosensing up-regulates histone deacetylases and prevents epigenetic response as well as osteogenic fate determination. Interestingly, we see similar defective nuclear mechanosensing in bone from patients with osteoarthritis, indicating that this cellular mechanism is likely relevant to bone-related diseases.