Regulating signaling and gene expression in tendon cells with mechanical load

Summary form only given. Tendons are designed to transfer the force of muscle contraction to bone to effect limb movement and are principally tensile load bearing. However, tendons may also be subjected to compression when passing through a pully, traveling under bone or are subjected to a deformation normal to the tensile load. Tendons are also subjected to shear as they glide through sheaths or extratendinous tissue, as collagen fibrils slide past one another during bending or as fluid flows amidst cells and fibrils during load bearing. Therefore, tendon cells are subjected to diverse mechanical loading during routine use, injury, overuse and even iatrogenically. Our lab has focused on tendon cell responses to mechanical loading in several different models in vivo, ex vivo and in vitro in both 2D and 3D models. Cells in each experimental model respond to applied load by signaling, initially, through an increase in intracellular calcium followed by downstream pathway activation. Cells may also act synergistically with a ligand to increase or decrease a response to load. IL-lb can act as a positive stimulus whereas ATP and perhaps other purines, may act as a negative modulator of a load response. Moreover, cells have multiple mechanisms with which to respond to load including integrin contacts with extracellular matrix, cell-cell contacts at desmosomes, intracellular contractile proteins including actin but also titin and nebulin, classically associated with muscle. We discuss the loading paradigms as well as cellular responses in tendon cells in the above models.