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PubMed1985

Characterization of chicken skeletal muscle myosin light chain kinase. Evidence for muscle-specific isozymes.

Myosin light chain kinase purified from chicken white skeletal muscle (Mr = 150,000) was significantly larger than both rabbit skeletal (Mr = 87,000) and chicken gizzard smooth (Mr = 130,000) muscle myosin light chain kinases, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Km and Vmax values with rabbit or chicken skeletal, bovine cardiac, and chicken gizzard smooth muscle myosin P-light chains were very similar for the chicken and rabbit skeletal muscle myosin light chain kinases. In contrast, comparable Km and Vmax data for the chicken gizzard smooth muscle myosin light chain kinase showed that this enzyme was catalytically very different from the two skeletal muscle kinases. Affinity-purified antibodies to rabbit skeletal muscle myosin light chain kinase cross-reacted with chicken skeletal muscle myosin light chain kinase, but the titer of cross-reacting antibodies was approximately 20-fold less than the anti-rabbit skeletal muscle myosin light chain kinase titer. There was no detectable antibody cross-reactivity against chicken gizzard myosin light chain kinase. Proteolytic digestion followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis or high performance liquid chromatography showed that these enzymes are structurally very different with few, if any, overlapping peptides. These data suggest that, although chicken skeletal muscle myosin light chain kinase is catalytically very similar to rabbit skeletal muscle myosin light chain kinase, the two enzymes have different primary sequences. The two skeletal muscle myosin light chain kinases appear to be more similar to each other than either is to chicken gizzard smooth muscle myosin light chain kinase.

Animals↗
PubMed1995

Influence of muscle length on work from trabecular muscle of frog atrium and ventricle.

The work capacity of segments of atrial and ventricular muscle from the frog Rana pipiens was measured as a function of muscle length using the work loop technique. Both the work done during shortening and the work required to re-lengthen the muscle after shortening increased with muscle length. Net work increased with length up to a maximum, beyond which work declined. The optimum sarcomere length for work output was 2.5-2.6 microns for both atrial and ventricular muscle. Isometric force increased with muscle length to lengths well beyond the optimum for work output. Thus, the decline in work at long lengths is not simply a consequence of a reduction in the capacity of heart muscle to generate force. It is proposed that it is the non-linear increase in work required to re-lengthen muscle with increasing muscle length which limits net work output and leads to a maximum in the relationship between net work and muscle length. Extension of the results from muscle strips to intact hearts suggests that the work required to fill the ventricle exceeds that available from atrial muscle at all but rather short ventricular muscle lengths.

Animals↗
PubMed1994

Muscle fiber splitting in stretch-enlarged avian muscle.

This study examined the role of longitudinal fiber splitting in enlarged anterior latissimus dorsi (ALD) muscle of adult quail. Muscle hypertrophy was induced using a model of progressive stretch overload (PSO) (5). After 16 and 28 d of PSO, muscle mass in the stretched ALD muscle increased significantly (P < 0.05) 188% and 294%, respectively, when compared with the intra-animal control muscle. Muscle length increased significantly (P < 0.05) in the stretched ALD muscle vs the intra-animal control by approximately 77% for both groups. Fiber number, which was assessed using direct counts after nitric acid digestion, did not change in the 16-d group; however, the 28-d stretched ALD muscle exhibited a 30% increase (P < 0.05) in fiber number vs the intra-animal control muscle. Furthermore, the frequency of splitting (i.e., branching) fibers was less than 0.3% in all muscles examined except the 28-d stretched ALD muscle. The 28-d stretched ALD muscle had 5.25% of its muscle fibers exhibiting split profiles. These results demonstrate that PSO produces effects unlike chronic stretch overload in that longitudinal fiber splitting may contribute significantly to an increase in fiber number.

Adaptation, Physiological↗
PubMed1995

Muscle-specific enzyme activity patterns of the capillary bed of human oro-facial, masticatory and limb muscles.

Enzyme-histochemical methods were used to analyse the activities of alkaline phosphatase (AP), dipeptidylpeptidase IV (DPP IV) and adenosine triphosphatase (ATPase) in capillaries of four different human oro-facial muscles, the major and minor zygomatic, the orbicularis oris and buccinator, one masticatory, the masseter and two limb muscles, the biceps brachii and first dorsal interosseus muscles. In all muscles, except for the orbicularis oris, the majority of the capillaries lacked enzyme activity. Therefore, none of these enzymes seems to be reliable as a general marker for human muscle capillaries. In general, the capillaries of the limb muscles and the major and minor zygomatic and the buccinator, were similar in their staining pattern for AP and ATPase, but differed in DPP IV staining. The orbicularis oris muscle differed from the other muscles by showing the largest proportion of capillaries with AP and ATPase activity. The masseter muscle had the largest proportion of capillaries stained for DPP IV. The muscle specific differences in enzyme activity of the capillaries are in agreement with our previous findings of specific differences between limb, oro-facial and masticatory muscles with respect to capillary supply and composition of fibre types and myosins. The results reflect functional specialization of the capillary bed of human muscles.

Adenosine Triphosphatases↗
PubMed1995

Delayed muscle soreness. The inflammatory response to muscle injury and its clinical implications.

Delayed onset muscle soreness (DOMS) is a sensation of discomfort that occurs 1 to 2 days after exercise. The soreness has been reported to be most evident at the muscle/tendon junction initially, and then spreading throughout the muscle. The muscle activity which causes the most soreness and injury to the muscle is eccentric activity. The injury to the muscle has been well described but the mechanism underlying the injury is not fully understood. Some recent studies have focused on the role of the cytoskeleton and its contribution to the sarcomere injury. Although little has been confirmed regarding the mechanisms involved in the production of delayed muscle soreness, it has been suggested that the soreness may occur as a result of mechanical factors or it may be biochemical in nature. To date, there appears to be no relationship between the development of soreness and the loss of muscle strength, in that the timing of the two events is different. Loss of muscle force has been observed immediately after the exercise. However, by collecting data at more frequent intervals a second loss of force has been reported in mice 1 to 3 days post-exercise. Future studies with humans may find this second loss of force to be related to DOMS. The role of inflammation during exercise-induced muscle injury has not been clearly defined. It is possible that the inflammatory response may be responsible for initiating, amplifying, and/or resolving skeletal muscle injury. Evidence from the literature of the involvement of cytokines, complement, neutrophils, monocytes and macrophages in the acute phase response are presented in this review. Clinically, DOMS is a common but self-limiting condition that usually requires no treatment. Most exercise enthusiasts are familiar with its symptoms. However, where a muscle has been immobilised or debilitated, it is not known how that muscle will respond to exercise, especially eccentric activity.

Cytokines↗
PubMed1993

Promotion of muscle regeneration in the toad (Bufo viridis) gastrocnemius muscle by low-energy laser irradiation.

The effect of low-energy laser (He-Ne) irradiation on the process of skeletal muscle regeneration after cold injury to the gastrocnemius muscle of the toad (Bufo viridis) was studied using quantitative histological and morphometric methods. The injured zones in the experimental toads were subjected to five direct He-Ne laser (632.8 nm wavelength) irradiations (6.0 mW for 2.3 min) every alternate day starting on the fourth day postinjury. Muscles that were injured as above, and subjected to red-light irradiation, served as a control group. Morphometric analysis was performed on histological sections of injured areas at 9, 14, and 30 days postinjury. At 9 days postinjury, mononucleated cells populated 69.3% +/- 16.8% of the total area of injury. Thereafter, their volume fraction (percent of total injured zone) decreased gradually but more rapidly in the laser-irradiated muscle than in the control. The volume fraction of the myotubes in the laser-irradiated muscles at 9 days of muscle regeneration was significantly higher (7.0% +/- 2.2%) than in the control muscle (1.2% +/- 0.4%). Young myofibers in the laser-irradiated muscles populated 15.5% +/- 7.9% and 65.0% +/- 9.5% of the injured area at 9 and 14 days of muscle regeneration, respectively, while in control muscles these structures were not evident at 9 days and made up only 5.3% +/- 2.9% of the traumatized area at 14 days postinjury. The volume fraction of the young myofibers further increased by 30 days of muscle regeneration making up 75.7% +/- 13.2% of the traumatized area, while in the laser-irradiated muscles most of the injured zone was filled with mature muscle fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Gemelli and obturator internus muscles: different heads of one muscle?

BACKGROUND: The superior gemellus, inferior gemellus, and obturator internus muscles were once regarded as a single muscle judging from their insertion and function. However, current textbooks of anatomy do not treat them as one muscle. In gross anatomy, the classification of muscles depends largely upon the nerve supply, so that the present author re-examined the nerve supply to the three muscles. METHODS: Fourteen nerve-muscle specimens were taken from 12 cadavers (five males and seven females) and examined with the unaided eye and under a dissecting microscope. RESULTS: (1) The modes of nerve supply to the superior gemellus, inferior gemellus, and obturator internus muscles differed; however, the nerves to the muscles shared the same spinal nerve components. (2) The gemelli formed a muscular pocket ("gemellus pocket") through which obturator internus muscle passed. CONCLUSIONS: In light of this knowledge on nerve muscle relationships, the difference in the pattern of nerve supply to the superior gemellus, inferior gemellus, and obturator internus muscles cannot be the basis for stating that the muscle are independent. Rather, their fusion to form the gemellus pocket and their common insertion suggest that they are different heads of one muscle.

Aged↗
PubMed1993

Suboccipital muscles in the cat neck: morphometry and histochemistry of the rectus capitis muscle complex.

The morphometry, histochemistry, and biomechanical relationships of rectus capitis muscles were examined in adult cats. This family of muscles contained six members on the dorsal, ventral, and lateral aspects of the upper cervical vertebral column. Three dorsal muscles (rectus capitis posterior major, medius, and minor) formed a layered complex spanning from C1 and C2 to the skull. Rectus capitis posterior major was composed predominantly of fast fibers, but the other two deeper muscles contained progressively higher proportions of slow fibers. One ventral muscle, rectus capitis anterior major, was architecturally complex. It originated from several cervical vertebrae and appeared to be divided into two different heads. In contrast, rectus capitis anterior minor and rectus capitis lateralis were short, parallel-fibered muscles spanning between the skull and C1. The ventral muscles all had nonuniform distributions of muscle-fiber types in which fast fibers predominated. Dorsal and ventral muscle groupings usually had cross-sectional areas of 0.5 cm2 or more, reflecting a potential capacity to generate maximal tetanic force in excess of 9 N. Biomechanical analyses suggested that one muscle, rectus capitis lateralis, had its largest moment in lateral flexion, whereas the other muscles had large, posturally dependent moment arms appropriate for actions in flexion-extension. The observation that most rectus muscles have relatively large cross-sectional areas and high fast-fiber proportions suggests that the muscles may have important phasic as well as postural roles during head movement.

Animals↗
PubMed1991

Functionally complex muscles of the cat hindlimb. V. The roles of histochemical fiber-type regionalization and mechanical heterogeneity in differential muscle activation.

Several cat hindlimb muscles that exhibit differential activation (activity that is restricted to a specific region of muscle) during natural movements were studied to determine the possible roles of 1) non-uniform distribution of histochemically-identified muscle fiber-types (semitendinosus, ST; tibialis anterior, TA) or 2) mechanical heterogeneity (biceps femoris, BF; tensor fasciae latae, TFL). Using chronic recording techniques, electromyographic (EMG) activity was recorded from multiple sites of each muscle during treadmill locomotion, ear scratch, and paw shake. Standard histochemical analysis was performed on each muscle to determine fiber-type distribution. The histochemically regionalized muscles (ST and TA) were differentially active during slow locomotion; the deep regions (high in type I [SO] fibers) were active, but the superficial regions (high in type IIB [FG] fibers) were inactive. Vigorous movements (fast locomotion, ear scratch, paw shake) produced additional, synchronous activation of the superficial regions. In all movements, ST and TA activation patterns were consistent with the existence of identically timed synaptic inputs to all motoneurons within each motoneuron pool, resulting in an orderly recruitment of each whole pool. The differential activation recorded from ST and TA during slow locomotion was presumably a consequence of the non-uniform distribution of the different muscle fiber types. In contrast, differential activation of the histochemically nonregionalized, mechanically heterogeneous muscles (BF and TFL) resulted from non-synchronous activation of different muscle regions. The selective activation of BF or TFL compartments was indicative of differential synaptic inputs to, and selective recruitment of, subpopulations of the motoneuron pool, with each motoneuron subpopulation exclusively innervating physically separate regions of the muscle consistent with the regions defined by the neuromuscular territories of the major nerve branches supplying each muscle. Individual neuromuscular compartments of BF and TFL differ in their mechanical arrangements to the skeleton and in their contribution to mechanical action(s) at the hip and knee joints. Selective neural activation of mechanically distinct compartments within a mechanically heterogeneous muscle can provide highly advantageous mechanical "options" for animals that perform kinematically diverse movements. With regard to EMG recording techniques, the results of this study emphasize the need for carefully chosen EMG sampling sites and the value of knowing the muscle histochemistry, neuromuscular and musculoskeletal anatomy and possible mechanical functions prior to recording EMG.

Adenosine Triphosphatases↗
PubMed1991

Distribution patterns of muscle fibre types in major muscles of the bull (Bos taurus).

The study describes the variations in distribution and cross-sectional area (fibre size) of three muscle fibre types (I, IIA, IIB) in 34 of the largest muscles of the bull (Bos taurus). The animals had been kept strictly unexercised for one year before slaughter. Representative sampling was done at 15 positions within each muscle, and from 2700 to 4500 fibres were analysed in each muscle. Different intermuscular patterns are described. The overall volume fraction (%) of type I fibres was about 10% higher in the forepart muscles than in the hindpart muscles (41% and 31%, respectively), while the mean content of type IIB fibres was similar. Type I fibres were particularly abundant in antigravity muscles. Of these, the hindlimb muscles contained 50% more type I fibres (by weight) than those of the forelimb. Typical antigravity antagonists contained very few type I fibres. In the thigh cross-section the proportion of type I fibres was highest in the anterior and medial parts, while the IIB fibres tended to be concentrated in the superficial and posterior parts. Intramuscular patterns were revealed, with type I fibres becoming gradually more abundant from superficial to deep regions, while IIB fibres had an opposite distribution. This was particularly evident in the thigh proper and in the scapular region. Within each fasciculus of all the muscles, the muscle fibre types formed a general spatial pattern. Type I fibres in the muscles of the forepart were on average about 15% larger than those of the muscles in the hindpart. The IIB fibres were on average about 10% larger in the hindpart than in the forepart muscles. A covariation between the proportion of type I and IIB fibres and their cross-sectional area was indicated.

Adenosine Triphosphatases↗
PubMed1988

The effect of sepsis in rats on skeletal muscle protein synthesis in vivo and in periphery and central core of incubated muscle preparations in vitro.

Recent studies demonstrated the development of a central, hypoxic core in incubated rat skeletal muscles. The influence of a central core on changes in protein synthesis rate, observed in incubated muscles from septic rats, is not known. In the present study, intact soleus muscles from 40 to 60-g sham-operated control rats and from septic rats (16 hours after cecal ligation and puncture) were incubated in vitro in a flaccid or stretched state. Protein synthesis rate was determined in whole muscle and in the central core and periphery of the muscle by measuring incorporation of 14C-phenylalanine into protein. Protein synthesis rate in vivo was measured with a flooding-dose technique using 3H-phenylalanine. The development of a central, hypoxic core in incubated muscles was assessed histochemically by staining the muscles for alpha-glucan phosphorylase activity. A central core with loss of alpha-glucan phosphorylase activity was noted after incubation for 30 minutes in both control and septic muscles. The protein synthesis rate was lower in the central core than in the periphery of incubated flaccid control muscles. In all other in vitro muscle preparations, however, there were no significant differences in protein synthesis rate among whole muscles, central core and periphery. Protein synthesis rate in septic muscles was reduced to a similar extent, approximately 20%, in vivo and in the different in vitro preparations, both when measured in whole muscle and in the central core or periphery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

An animal model for human masseter muscle: histochemical characterization of mouse, rat, rabbit, cat, dog, pig, and cow masseter muscle.

The masseter muscle of several animal species was investigated by use of a histochemical method for the demonstration of acid-stable and alkali-stable myosin adenosine triphosphatase (ATPase). The following subdivisions of fiber types were used: Type I fibers show weak ATPase activity at pH 9.4, type IM fibers react moderately, and type II fibers react strongly. Rat and mouse masseter muscles contained type II fibers only, as did some rabbit masseter muscles, whereas other rabbit masseter muscles possessed equal amounts of type I and II fibers. Cat and dog masseter muscles possessed both type II and I fibers, with type II predominating. Cow masseter muscle consisted mainly of type I fibers, although some cow masseter muscles contained a very small number of type II fibers. Pig masseter muscle had both type I, II, and IM fibers. One of the characteristics of human masseter muscle is type IM fibers, which are rarely seen in muscles other than the masticatory muscles. Therefore, pig masseter muscle might be a suitable animal model for experimental studies, such as an investigation of the distribution and diameter of fiber types in the masticatory muscles before and after orthognathic surgery.

Adenosine Triphosphatases↗
PubMed2003

Regeneration of transgenic skeletal muscles with altered timing of expression of the basic helix-loop-helix muscle regulatory factor MRF4.

In regenerating muscle cells, muscle regulatory factor (MRF) 4 is normally the last of the four MRFs to be expressed. To analyze how the timing of MRF4 expression affects muscle regeneration, we compared regeneration after local freeze injury of muscles from wild-type mice with muscles from transgenic mice in which MRF4 expression was under control of an approximately 1.6-kb fragment of the myogenin promoter. Three days after injury, masseter and tibialis anterior (TA) muscles in wild-type mice expressed little or no MRF4 mRNA; whereas these muscles in transgenic mice expressed abundant MRF4 mRNA from both the transgene and the endogenous gene. Thus, MRF4 up-regulation was accelerated in transgenic compared to wild-type regenerating muscles, and expression of the transgene appeared to activate, perhaps indirectly, expression of the endogenous MRF4 gene. At 11 days after injury, regeneration, as measured by cross-sectional area and density of regenerated fibers, was significantly impaired in transgenic TA compared to wild-type TA, whereas at 19 days after injury both transgenic and TA muscle fibers had fully recovered to preinjury values. Regeneration of masseter muscles, which normally regenerate much less completely than TA muscles, was unaffected by the transgene. Thus, the timing of MRF4 up-regulation, as well as additional muscle-specific factors, can determine the progress of muscle regeneration.

Animals↗
PubMed2003

A computational model for the adaptation of muscle and tendon length to average muscle length and minimum tendon strain.

This paper hypothesizes that average muscle length and minimum tendon strain govern muscle and tendon length adaptation in all situations. A model has been implemented to test this hypothesis, and simulations have been performed for normal development, bone lengthening, immobilization, and retinacular release experiments in young and adult animals. The simulation results predict that both muscle and tendon lengthen during normal development, with the rate of tendon growth slowing faster than the rate of muscle growth. The results also predict that muscle length increases during bone lengthening in both young and adult animals, while tendon length increases only in young animals. For immobilization in adult animals, the results predict that muscle length increases when the muscle is immobilized in a lengthened position and decreases when the muscle is immobilized in a shortened position with no change in tendon length. For immobilization in young animals, the results predict reduced muscle growth and increased tendon growth regardless of immobilization position. Finally, the simulations predict that retinacular release which increases excursion of the musculotendinous unit leads to increased muscle length with decreased tendon length in young animals and decreased muscle length with no change in tendon length in adult animals. These simulation results are consistent with experimental findings reported in the literature by other investigators. This suggests that average muscle length and minimum tendon strain may represent general principles that govern muscle and tendon length adaptation.

Adaptation, Physiological↗
PubMed2002

Anomalous lumbrical muscles arising from the deep surface of flexor digitorum superficialis muscles in man.

During anatomy practice in 1999 at Kumamoto University School of Medicine, the anomalous lumbrical muscles originating in the forearm were observed in both arms of a cadaver. These muscles, originating from the intermediate tendon of the deep layer of the flexor digitorum superficialis for the index finger (FDS-II), passed through the carpal tunnel to join the insertion of the first lumbrical muscle, and formed a muscle belly near the origin in the left and at the insertion in the right. The left anomalous muscle was innervated by a branch of the median nerve just proximal to the carpal tunnel. The right one received a twig from the nerve to the first lumbrical muscle. Tracing the nerve fibers by peeling off the epi- and perineurium clarified that the nerve fibers supplying the left anomalous muscle formed a common bundle with the fibers to the first lumbrical muscle. Therefore, these anomalous muscles are considered to be the accessory lumbrical muscles arising from the forearm. The three accessory lumbricalis, including one case reported by Yamada (1986), received branches which had slightly different origins from proximally (nerve to the distal belly of FDS-II) to distally (nerve to the first lumbricalis). Accordingly the position of the muscle belly shifted distally. The occurrence of these unusual accessory lumbrical muscles indicates that the distal belly of FDS-III and the first lumbricalis are derived from a common muscle origin and presents an important clue to the phylogenetic origin of the flexor digitorum superficialis.

Aged↗
PubMed1997

Combined bilateral superior rectus muscle recession and inferior oblique muscle weakening for dissociated vertical deviation.

PURPOSE: Dissociated vertical deviation (DVD) is a common disorder that is often difficult to treat satisfactorily with extraocular muscle surgery. Weakening both elevators in a single eye is uncommonly performed because of possible severe upgaze deficiency or chin-up head posture postoperatively. METHODS: A retrospective review of medical records was performed that yielded 14 patients who had undergone bilateral superior rectus muscle recessions (mean 8.1 mm, range 5-10 mm) and bilateral inferior oblique muscle recession, myectomy, or anterior transposition in the treatment of DVD. Three additional patients with asymmetric inferior oblique muscle overaction or true hypertropia in primary gaze position were identified who had bilateral superior rectus muscle recessions combined with unilateral inferior oblique muscle weakening. RESULTS: Mild-to-moderate elevation deficiencies were common postoperatively but never exceeded -2 up-gaze limitation (scale 0 to -4) except in the immediate postoperative period and were not associated with persistent chin-up head posturing. Cosmetically objectionable upper eyelid retraction occurred in one patient after re-recession of a superior rectus muscle but before inferior oblique muscle surgery. Only three patients undergoing four vertical muscle surgeries had residual DVD >10 PD in primary gaze position, and none exhibited manifest dissociated strabismus warranting further treatment. CONCLUSION: Bilateral superior rectus muscle recession of up to 10 mm combined with inferior oblique muscle weakening appears to be a safe surgical approach in the management of patients with large angle or recurrent DVD. Our data further suggest that simultaneous four vertical muscle surgery may be preferred in some patients to weakening the superior rectus or inferior oblique muscles alone.

Depth Perception↗
PubMed1999

Changes in muscle mass and phenotype and the expression of autocrine and systemic growth factors by muscle in response to stretch and overload.

The study of the underlying mechanisms by which cells respond to mechanical stimuli, i.e. the link between the mechanical stimulus and gene expression, represents a new and important area in the morphological sciences. Several cell types ('mechanocytes'), e.g. osteoblasts and fibroblasts as well as smooth, cardiac and skeletal muscle cells are activated by mechanical strain and there is now mounting evidence that this involves the cytoskeleton. Muscle offers one of the best opportunities for studying this type of mechanotransduction as the mechanical activity generated by and imposed upon muscle tissue can be accurately controlled and measured in both in vitro and in vivo systems. Muscle is highly responsive to changes in functional demands. Overload leads to hypertrophy, whilst decreased load force generation and immobilisation with the muscle in the shortened position leads to atrophy. For instance it has been shown that stretch is an important mechanical signal for the production of more actin and myosin filaments and the addition of new sarcomeres in series and in parallel. This is preceded by upregulation of transcription of the appropriate genes some of which such as the myosin isoforms markedly change the muscle phenotype. Indeed, the switch in the expression induced by mechanical activity of myosin heavy chain genes which encode different molecular motors is a means via which the tissue adapts to a given type of physical activity. As far as increase in mass is concerned, our group have cloned the cDNA of a splice variant of IGF-1 that is produced by active muscle that appears to be the factor that controls local tissue repair, maintenance and remodelling. From its sequence it can be seen that it is derived from the IGF-1 gene by alternative splicing but it has different exons to the liver isoforms. It has a 52 base insert in the E domain which alters the reading frame of the 3' end. Therefore, this splice variant of IGF-1 is likely to bind to a different binding protein which exists in the interstitial tissue spaces of muscle, neuronal tissue and bone. This would be expected to localise its action as it would be unstable in the unbound form which is important as its production would not disturb the glucose homeostasis unduly. This new growth factor has been called mechano growth factor (MGF) to distinguish it from the liver IGFs which have a systemic mode of action. Although the liver is usually thought of as the source of circulating IGF-1, it has recently been shown that during exercise skeletal muscle not only produces much of the circulating IGF-1 but active musculature also utilises most of the IGF-I produced. We have cloned both an autocrine and endocrine IGF-1, both of which are upregulated in cardiac as well as skeletal muscle when subjected to overload. It has been shown that, in contrast to normal muscle, MGF is not detectable in dystrophic mdx muscles even when subjected to stretch and stretch combined with electrical stimulation. This is true for muscular dystrophies that are due to the lack of dystrophin (X-linked) and due to a laminin deficiency (autosomal), thus indicating that the dystrophin cytoskeletal complex may be involved in the mechanotransduction mechanism. When this complex is defective the necessary systemic as well as autocrine IGF-1 growth factors required for local repair are not produced and the ensuing cell death results in progressive loss of muscle mass. The discovery of the locally produced IGF-1 appears to provide the link between the mechanical stimulus and the activation of gene expression.

Adaptation, Physiological↗
PubMed2001

Dermal fibroblasts participate in the formation of new muscle fibres when implanted into regenerating normal mouse muscle.

Both in vitro and in vivo studies have described the conversion of fibroblasts to myogenesis when in the presence of dysfunctional myogenic cells. Myogenic conversion of fibroblasts subjected to a normal, as opposed to a diseased muscle environment has only been reported in vitro. The primary aim of this work was to determine if fibroblasts can convert to a myogenic lineage and contribute to new fibre formation when implanted into the regenerating muscle of a normal mouse. Dermal fibroblasts were prepared from neonatal mouse skin and labelled prior to implantation with the fluorescent nuclear marker 4',6-diamidino-2-phenylindole (DAPI). Cells were implanted into muscles of host mice that had been subjected to either cold/crush or minced muscle injury. Some host muscles were x-irradiated to deplete the muscle of endogenous muscle precursor cells. Muscles were removed at 3 wk postimplantation and analysed both histologically and for the presence of DAPI labelled nuclei. Fibres containing DAPI labelled central nuclei indicated that the implanted cells had participated in the regenerative process. Mouse dermal fibroblasts therefore do contribute to muscle fibre formation in regenerating normal mouse muscle but the extent of their contribution is dependent on the nature of the trauma induced in the host muscle. The study also showed that regeneration was more successful in muscles which had not been irradiated, which is contrary to the previous studies where dermal fibroblasts were introduced into myopathic mouse muscle.

Animals↗