Relation between myofibers and connective tissue during muscle injury repair.

The connective tissue framework in skeletal muscle combines the contractile myofibers into a functional unit, in which the contraction of myofibers is transformed into movement via myotendinous junctions (MTJs) at their ends, where myofibers attach to tendons/fascia. The cytoskeletal contractile myofilament apparatus adheres through subsarcolemmal and transmembrane molecules to the surrounding extracellular matrix, with integrin and dystrophin associated chains of molecules being the two main adhesion complexes. In shearing type of muscle injury both myofibers and the connective tissue framework are ruptured and thereby the functional tendon-muscle-tendon units are disrupted. The stumps of the ruptured myofibers are separated and at the same time joined by a connective tissue scar, through which the ends of regenerating myofibers try to pierce, but as the scar becomes more compact the ends attach to the scar by new mini-MTJs. During the early phase ruptured myofibers try to compensate for the lost MTJ attachment by reinforcing their integrin mediated lateral adhesion, which returns to normal low level after formation of the mini-MTJs and at which time complementary increase of dystrophin and associated molecules on lateral sarcolemma takes place. The stumps appear to remain separated by and attached to the interposed scar for many months, possibly for ever, i.e. the original tendon-muscle-tendon units may have become permanently divided into two consecutive units. Remarkably, axon sprouts are able to penetrate through the interposed scar to form new neuromuscular junctions on those abjunctional stumps which were denervated by the rupture.