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.
Intermediate filament (IF) proteins show specific spatial and temporal expression during development of skeletal muscle. Nestin, the least known muscle IF, has an important role in neuronal regeneration. Therefore, we analyzed the expression pattern of nestin as related to that of vimentin and desmin during skeletal muscle regeneration. Nestin and vimentin appear at 6 h post-injury in myoblasts, with maximum expression around day 3-5 post-injury. Thereafter, vimentin expression ceases completely, whereas that of nestin is downregulated to remain only in the sarcoplasm next to neuromuscular and myotendinous junctions. Desmin appears at 6-12 h post-injury and becomes the predominant IF in myofibers simultaneously with the appearance of cross-striations. The expression pattern and colocalization of nestin and vimentin, known to form heteropolymers, suggests that they are essential during the early dynamic phase of the myofiber regeneration when migration, fusion, and structural modeling of myogenic cells occurs, whereas desmin is responsible for keeping myofibrils in register in mature myofibers. In conclusion, the expression of nestin is dynamically orchestrated with that of vimentin and desmin during skeletal muscle regeneration and recapitulates that seen during myogenesis, i.e. these IFs have key functional roles in the construction and restoration of skeletal myofibers.
Therapeutic ultrasound is used by many in the treatment of muscle injuries, but no previous attempts to objectively assess its effects on regenerating skeletal myofibers have been published. In this descriptive study, we followed the regeneration of contusion injury to the rat gastrocnemius muscle during treatment with pulsed ultrasound. The speed of myoregeneration in ultrasound-treated animals was compared with that in control animals by immunohistochemical, morphometric, and scintigraphic analyses. Although satellite cell proliferation was enhanced significantly (up to 96%) by the ultrasound treatment during the early stages of regeneration, there was no such effect on myotube production. The period of rapid fibroblast proliferation was extended from 3 to 4 days in the control group to 7 to 10 days in the ultrasound therapy groups, whereas recapillarization was virtually unaffected. We conclude that although treatment with pulsed ultrasound can promote the satellite cell proliferation phase of the myoregeneration, it does not seem to have significant effects on the overall morphological manifestations of muscle regeneration.
The intermediate filament proteins nestin, vimentin, and desmin show a specific temporal expression pattern during the development of myofibers from myogenic precursor cells. Nestin and vimentin are actively expressed during early developmental stages to be later down-regulated, vimentin completely and nestin to minimal levels, whereas desmin expression begins later and is maintained in mature myofibers, in which desmin participates in maintaining structural integrity. In this study we have analyzed the expression levels and distribution pattern of nestin in intact and denervated muscle in rat and in human. Nestin immunoreactivity was specifically and focally localized in the sarcoplasm underneath neuromuscular junctions (NMJs) and in the vicinity of the myotendinous junctions (MTJs), ie, in regions associated with acetylcholine receptors (AChRs). This association prompted us to analyze nestin in neurogenically and myogenically denervated muscle. Immunoblot analysis disclosed a marked overall increase of accumulated nestin protein. Similar to the extrajunctional redistribution of AChRs in denervated myofibers, nestin immunoreactivity extended widely beyond the NMJ region. Re-innervation caused complete reversion of these changes. Our study demonstrates that the expression levels and distribution pattern of nestin are regulated by innervation, ie, signal transduction into myofibers.
The tension-band wire technique seems to give good results in the treatment of proximal metaphysial/diaphysial fractures of the fifth metatarsal in cases of primary unsuccessful nonoperative treatment or primary unsuccessful intramedullary screw fixation.
We review new data derived from careful dissection studies on the macroscopic anatomy, innervation and function of the lumbar muscles, as well as information on the fibres in these muscles. The new findings correct previous misconceptions of the functional anatomy of the lumbar muscles. The innervation and function of the erector spinae and multifidus muscles are so different that they cannot be classified as a single unit. The new interpretation of the innervation of multifidus muscle is of importance, for example, for the neurophysiological examination of the lumbar muscles. The relative number of the slow and fast type of muscle fibres in lumbar muscles varies considerably, and selective atrophy of the fast fibres seems to ensue from inactivity, not only in patients with back pain but also in sedentary controls. The atrophy may be corrected by adequate exercise. Both the fibre type composition and degree of atrophy may well influence a person's susceptibility to low back pain arising from the muscles.
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