Epigenetic regulation of chondrocytes affected by mitochondria through mechanotransduction in osteoarthritis

Abnormal mechanical loading of articular cartilage is still considered an important pathogenic factor for osteoarthritis (OA). The occurrence and development of OA are accompanied by epigenetic alterations in chondrocytes. As the center of cellular energy metabolism, mitochondria have attracted increasing attention for their epigenetic regulation. Furthermore, mitochondria are mechanosensitive organelles, and abnormal mechanical loading affects chondrocyte epigenetics through the mitochondria, which may be one of the important mechanisms of OA pathogenesis. Well-known mitochondrial metabolites such as acetyl-CoA and α-ketoglutaric acid (α-KG) can be used as cofactors of histone modifying enzymes. Some histone modifying enzymes of lysine specific demethylase (KDMs) family are affected by mitochondrial function. In addition, TCA enzymes in mitochondria can undergo nuclear translocation and help regulate histone modification by catalyzing the generation of corresponding downstream products in the nucleus. However, the specific mechanism of mitochondrial epigenetic regulation of OA progression through chondrocytes remains unclear. Here, we discuss the changes in OA chondrocytes, their physiological activities under the conditions of physiological and supraphysiological mechanical loading, and the potential epigenetic regulation of mechanical loading through chondrocyte mitochondria. The combination of mechanobiological and epigenetic regulation mechanisms will provide new ideas and insights for the prevention and treatment of OA