Myotendinous Junction development and repair
Abstract
The myotendinous junction (MTJ) is the critical interface connecting muscle to tendon, enabling force transmission for movement and serving as the primary site of muscle injuries. Despite research into MTJ repair, treatment outcomes are suboptimal, partly due to the absence of a comprehensive synthesis of its structural components, cellular diversity, and developmental mechanisms, which impedes the rational selection of materials, cells, and regulatory factors for effective regeneration. This review synthesizes current knowledge on the cytoskeletal and extracellular matrix (ECM) architecture of the MTJ, the cell types involved in its development and repair, and the key molecular regulators governing its formation. We describe the hierarchical architecture of the MTJ and the key molecular complexes that mediate the mechanical connection between the muscle and the tendon. We also describe the roles of Col22a1-expressing muscle nuclei and various resident stem/progenitor cells in MTJ maintenance and healing. We discuss essential regulatory signaling pathways, including Slit, LRT, and BMP4. Furthermore, we evaluate existing MTJ repair strategies. Based on a review of MTJ development and injury repair, we observe that current treatment approaches largely fail to incorporate key insights from MTJ development, particularly regarding stem/progenitor cells and regulatory signals. Therefore, we propose that tissue engineering techniques, by integrating MTJ-resident stem/progenitor…
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