The myotendinous junction (MTJ), where muscle meets tendon, is highly vulnerable to injury. MTJ damage accounts for the majority of sports injuries; however, little is currently known about the detailed structure of the MTJ at the level of individual myofibres. Insights into MTJ architecture could uncover why this tissue is disproportionately affected by physical strain. In this study (Hoegsbjerg et al., 2025), Abigail Mackey and colleagues perform detailed three-dimensional imaging of single human muscle fibres at the MTJ, revealing an increased density of nuclei at the fibre tip. Both myonuclei (nuclei that occupy the same multinucleated myofibre) and, more unexpectedly, mononuclear cells accumulate at the MTJ. The authors find that the presence of mononuclear cells is particularly enhanced in type I myofibres relative to type II myofibres, highlighting structural differences between fibre types that might influence their fragility and ability to repair damage. Using RNAscope in situ hybridisation, they show that both myonuclei and mononuclear cells in the MTJ region express COL22A1, a collagen gene essential for stabilising the interface between muscle and tendon. Paradoxically, the highly complex tissue architecture observed at the MTJ suggests that it is designed to resist and repair damage and does not necessarily explain its vulnerability. A better understanding of the high number of individual cells present at the MTJ could enable new rehabilitation strategies to improve tissue repair and recovery following injury.
