Abstract
A critical link in the chain of force transmission from muscle fiber cross-bridge to bone is the interface between muscle and tendon-the myotendinous junction (MTJ). To meet the challenge of connecting these two tissues, the MTJ is specialized molecularly and morphologically. Distinct transcriptional profiles are evident for the myonuclei at the myofiber tips and a population of mononuclear tendon cells at the MTJ, demonstrating support from both sides in MTJ maintenance. Paradoxically, despite this high degree of specialization, the MTJ remains susceptible to strain (rupture) injury and is often associated with failed tissue healing. Incomplete understanding of the nature of the MTJ and the elements contributing to its plasticity hinder tackling this unsolved clinical challenge. The goal of this review is to summarize key structural and molecular features of the MTJ, discuss MTJ adaptation in response to mechanical (un)loading, aging, and injury, and highlight the major unanswered questions surrounding the MTJ.