Growth and Mechanical Adaptation of the Tendon-bone Enthesis

The growth of the vertebrate skeleton depends on the transmission of contractile muscle forces from tendon to bone, which is often accomplished across the extracellular matrix-rich enthesis. Little is known about how the enthesis responds to increased loading during postnatal growth. To study the cellular and matrix adaptations of the enthesis in response to increased muscle loading, we used optogenetics to induce skeletal muscle contraction and unilaterally load the Achilles tendon and enthesis in young mice. Daily bouts of unilateral optogenetic loading of the Achilles tendon in skeletally-immature mice led to reduced volume, radial expansion, and warping of the posterior calcaneus. These daily loading bouts also led to a mechanically weaker enthesis with increased molecular-level accumulation of collagen damage in the tendon. We identified mechanobiological pathways associated with increased loading and are exploring the molecular mechanisms that drive enthesis remodeling during perinatal growth in response to increased loading.