Extracellular matrix stiffening is a quintessential feature of cartilage aging, a leading cause of knee osteoarthritis. Yet, the downstream molecular and cellular consequences of age-related biophysical alterations are poorly understood. Here, we show that epigenetic regulation of α-Klotho represents a novel mechanosensitive mechanism by which the aged extracellular matrix influences chondrocyte physiology. Using mass spectrometry proteomics followed by a series of genetic and pharmacological manipulations, we discovered that increased matrix stiffness drove Klotho promoter methylation, downregulated Klotho gene expression, and accelerated chondrocyte senescence in vitro. In contrast, exposing aged chondrocytes to a soft matrix restored a more youthful phenotype in vitro and enhanced cartilage integrity in vivo. Our findings demonstrate that age-related alterations in extracellular matrix biophysical properties initiate pathogenic mechanotransductive signaling that promotes Klotho promoter methylation and compromises cellular health. These findings are likely to have broad implications even beyond cartilage for the field of aging research.
Three-dimensional (3D) bioprinting technology is now one of the best ways to generate new biomaterial for potential biomedical applications. Significant progress in this field since two decades ago has pointed the way toward use of natural biopolymers such as polysaccharides. Generally, these biopolymers such as alginate possess specific reactive groups such as carboxylate able to be chemically or enzymatically functionalized to generate very interesting hydrogel structures with biomedical applications in cell generation. This present review gives an overview of the main natural anionic polysaccharides and focuses on the description of the 3D bioprinting concept with the recent development of bioprinting processes using alginate as polysaccharide.
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