Molecular mechanisms of mechanical stress response during chondrogenesis

Muscloskeletal tissues, bone, cartilage, muscles and tendons regulate and support the body's actions and are differentiated from mesenchymal stem cells. These organs generate and/or respond to mechanical stress, which is inevitable in daily life. Among these tissues, cartilages play roles in articular function in joints where shear stress is loaded in combination with cyclical or intermittent compressive force by joint action, and provides a template for bone growth under compressive stress directed along the long axis of long bones. Along with soluble factors, such as cytokines and growth factors, mechanical stress has been recognized as one of the epigenetic factors that regulates the gene expression of various types of cells. Thus, the molecular mechanisms of the mechano-sensing, mechano-transduction, and mechano-response of cells have become a focus of connective tissue biology. Here, we will discuss the mechanisms through which differentiated chondrocytes and mesenchymal cells that are differentiating into chondrocytes respond to various types of mechanical stress by altering their phenotype and how these phenotypic changes are molecularly regulated. We will focus on the roles of cell-extracellular matrix interactions through integrins and downstream signaling pathways involving mitogen-activated protein kinases.