A glitch in the matrix: the pivotal role for extracellular matrix remodeling during muscle hypertrophy

Multinuclear muscle fibers are the most voluminous cells in skeletal muscle and the primary drivers of growth in response to loading. Outside the muscle fiber, however, is a diversity of mononuclear cell types that reside in the extracellular matrix (ECM). These muscle-resident cells are exercise-responsive and produce the scaffolding for successful myofibrillar growth. Without proper remodeling and maintenance of this ECM scaffolding, the ability to mount an appropriate response to resistance training in adult muscles is severely hindered. Complex cellular choreography takes place in muscles following a loading stimulus. These interactions have been recently revealed by single-cell explorations into muscle adaptation with loading. The intricate ballet of ECM remodeling involves collagen production from fibrogenic cells and ECM modifying signals initiated by satellite cells, immune cells, and the muscle fibers themselves. The acellular collagen-rich ECM is also a mechanical signal-transducer and rich repository of growth factors that may directly influence muscle fiber hypertrophy once liberated. Collectively, high levels of collagen expression, deposition, and turnover characterize a well-trained muscle phenotype. The purpose of this review is to highlight the most recent evidence for how the ECM and its cellular components affect loading-induced muscle hypertrophy. We also address how the muscle fiber may directly take part in ECM remodeling, and whether ECM dynamics are rate limiting for muscle fiber growth.

Automated summary

Multinuclear muscle fibers are the largest cells in skeletal muscle and play a crucial role in muscle growth. However, mononuclear cells in the extracellular matrix (ECM) also contribute to muscle hypertrophy. Proper remodeling and maintenance of the ECM is essential for an appropriate response to resistance training in adult muscles. The ECM remodeling process involves various cells and signals, and the acellular collagen-rich ECM acts as a mechanical signal transducer and repository of growth factors that influence muscle fiber hypertrophy. This review highlights the impact of the ECM and its cellular components on loading-induced muscle hypertrophy.