Relation between myofibers and connective tissue during muscle injury repair

Kääriäinen, Minna; Järvinen, Tero A.H.; Järvinen, Markku; Rantanen, Jussi; Kalimo, Hannu

doi:10.1034/j.1600-0838.2000.010006332.x

Cited by 162 publications

(156 citation statements)

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“…Our analysis begins to elucidate the role of Tcf4 + MCT fibroblasts in the transient MCT fibrosis characteristic of muscle regeneration. During regeneration, increased MCT maintains the structural and functional integrity of regenerating muscle (Kaariainen et al, 2000), orients forming myofibers (Sanes, 2004), and sequesters and presents growth factors necessary for satellite cells (Cornelison, 2008). However, excessive ECM during regeneration can impede mechanical function and hinder muscle regeneration (Huard et al, 2002;Sato et al, 2003).…”

Section: Pax7mentioning

confidence: 99%

Satellite cells, connective tissue fibroblasts and their interactions are crucial for muscle regeneration

et al. 2011

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SUMMARYMuscle regeneration requires the coordinated interaction of multiple cell types. Satellite cells have been implicated as the primary stem cell responsible for regenerating muscle, yet the necessity of these cells for regeneration has not been tested. Connective tissue fibroblasts also are likely to play a role in regeneration, as connective tissue fibrosis is a hallmark of regenerating muscle. However, the lack of molecular markers for these fibroblasts has precluded an investigation of their role. Using Tcf4, a newly identified fibroblast marker, and Pax7, a satellite cell marker, we found that after injury satellite cells and fibroblasts rapidly proliferate in close proximity to one another. To test the role of satellite cells and fibroblasts in muscle regeneration in vivo, we created Pax7CreERT2 and Tcf4 CreERT2 mice and crossed these to R26R DTA mice to genetically ablate satellite cells and fibroblasts. Ablation of satellite cells resulted in a complete loss of regenerated muscle, as well as misregulation of fibroblasts and a dramatic increase in connective tissue. Ablation of fibroblasts altered the dynamics of satellite cells, leading to premature satellite cell differentiation, depletion of the early pool of satellite cells, and smaller regenerated myofibers. Thus, we provide direct, genetic evidence that satellite cells are required for muscle regeneration and also identify resident fibroblasts as a novel and vital component of the niche regulating satellite cell expansion during regeneration. Furthermore, we demonstrate that reciprocal interactions between fibroblasts and satellite cells contribute significantly to efficient, effective muscle regeneration.

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Section: Pax7mentioning

confidence: 99%

Satellite cells, connective tissue fibroblasts and their interactions are crucial for muscle regeneration

et al. 2011

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“…However, in a variety of disease states, continued fibrosis contributes to the pathological process. In chronic myopathies and muscular dystrophies, fibrosis is considered to be associated with decreased strength and elasticity of muscle and may inhibit the diffusion of nutrients to myofibers (1)(2)(3). Identification of factors that regulate fibrosis is an important goal not only in understanding the pathogenesis of muscular dystrophies but also in developing novel therapies to treat these disorders.…”

mentioning

confidence: 99%

Myostatin Directly Regulates Skeletal Muscle Fibrosis

Kollias

Wagner

2008

Journal of Biological Chemistry

222

183

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Skeletal muscle fibrosis is a major pathological hallmark of chronic myopathies in which myofibers are replaced by progressive deposition of collagen and other extracellular matrix proteins produced by muscle fibroblasts. Recent studies have shown that in the absence of the endogenous muscle growth regulator myostatin, regeneration of muscle is enhanced, and muscle fibrosis is correspondingly reduced. We now demonstrate that myostatin not only regulates the growth of myocytes but also directly regulates muscle fibroblasts. Our results show that myostatin stimulates the proliferation of muscle fibroblasts and the production of extracellular matrix proteins both in vitro and in vivo. Further, muscle fibroblasts express myostatin and its putative receptor activin receptor IIB. Proliferation of muscle fibroblasts, induced by myostatin, involves the activation of Smad, p38 MAPK and Akt pathways. These results expand our understanding of the function of myostatin in muscle tissue and provide a potential target for anti-fibrotic therapies.Fibroblasts play an important role in the repair response of tissues to injury by secreting extracellular matrix proteins including collagen and growth factors. However, in a variety of disease states, continued fibrosis contributes to the pathological process. In chronic myopathies and muscular dystrophies, fibrosis is considered to be associated with decreased strength and elasticity of muscle and may inhibit the diffusion of nutrients to myofibers (1-3). Identification of factors that regulate fibrosis is an important goal not only in understanding the pathogenesis of muscular dystrophies but also in developing novel therapies to treat these disorders. Several potential future therapies for the muscular dystrophies, including those involving gene and myoblast transfer, may be hampered by significant fibrosis.Myostatin is a highly conserved transforming growth factor-␤ (TGF-␤) 2 family member that is expressed in skeletal muscle, which is also the primary target tissue (4). Deletion of the myostatin gene (MSTN) in mice leads to muscle hypertrophy and hyperplasia with an approximate doubling of muscle mass (4). This function of myostatin, as an endogenous inhibitor of muscle growth, is also conserved in humans, as demonstrated by the identification of a hypermuscular child with a loss-of-function mutation in the myostatin gene (5). One mechanism by which myostatin regulates muscle growth in adult animals appears to be direct inhibition of the proliferation and differentiation of resident muscle precursor cells (6 -8).The potential effect of myostatin inhibition on muscle degenerative diseases has been explored in various animal models. In the absence of myostatin, muscle regenerates more quickly and completely following acute and chronic injury (8, 9). In the mdx mouse, a model of Duchenne and Becker muscular dystrophy, myostatin deletion, or postnatal inhibition increases muscle mass and strength (10 -12). An early observation of mdx/mstn null mice was that the diaphragm muscle of t...

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“…Previous works also report greater injury occurrence at the myotendinous region 1,3 . This is explained by the fact that each muscular fiber is connected to its terminal regions by conjunctive tissue, and the contraction of the miofibers is transformed in movement, via myotendinous junction 23 . Thus, the lesion, which is observed more intensely at this area, may occur due to the concentration of stress at the distal region of the muscular fiber.…”

Section: Discussionmentioning

confidence: 99%

“…It is important to highlight that muscular regeneration and fibrosis formation at the injured area are competitive events and fibrosis may lead to complete inhibition of muscle regeneration 27 . In this case, physical therapeutic resources, such as mobilization, should be applyied during the process of muscle regeneration in order to prevent fibrosis formation 23 .…”

Section: Discussionmentioning

confidence: 99%

Regeneração do músculo tibial anterior em diferentes períodos após lesão por estimulação elétrica neuromuscular

Botelho

Facio

Minamoto

2007

Rev. bras. fisioter.

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Background: Skeletal muscle injuries may be caused by contraction of the muscle concerned. Objective: To analyze the tibialis anterior muscle at different times following injury induced by electrical stimulation. Method: Male Wistar rats (298.2 ± 16.0g) were divided into two electrically stimulated groups evaluated after three and five days (n= 20) and two control groups, also evaluated after three and five days (n= 14). While stretched, the tibialis anterior muscle was injured by neuromuscular electrical stimulation (90 minutes, 30 Hz, 1 m/s, Ton/Toff 4 s and 4 mA). Three and five days afterwards, the animals were sacrificed and the muscles were removed. Histological sections were cut (10 μm) using a cryostat and were stained with toluidine blue. The body and muscle weights were statistically analyzed using Student's t test (p≤ 0.05). Results: The final body weight was higher than the initial weight for the 3-day control group (288.5 ± 18.3g vs. 308.5 ± 24.3g) and 5-day control group (288.4 ± 15.0g vs. 305.5 ± 20.7g) and lower for the 3-day stimulated group (305.0 ± 13.0g vs. 285.6 ± 13.2g) and 5-day stimulated group (306.1 ± 12.4g vs. 278.4 ± 20.9g). The relative muscle weight in the 5-day stimulated group was lower than in the 5-day control group (0.20 ± 0.001% vs. 0.22 ± 0.01%, respectively). The histological analysis showed variance between the animals regarding the extent and signs of fiber damage and/or regeneration, and the distal region was the most injured. The 3-day stimulated group presented predominance of cell infiltrate and myofilament hypercontraction, while the 5-day stimulated group presented predominance of cell infiltrate, basophils and fibrosis. Conclusion: A period of two days following electrical stimulation was sufficient for showing a difference in the regeneration process. The distal region of the tibialis anterior muscle was more susceptible to injury.

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Relation between myofibers and connective tissue during muscle injury repair

Cited by 162 publications

References 0 publications

Satellite cells, connective tissue fibroblasts and their interactions are crucial for muscle regeneration

Satellite cells, connective tissue fibroblasts and their interactions are crucial for muscle regeneration

Myostatin Directly Regulates Skeletal Muscle Fibrosis

Regeneração do músculo tibial anterior em diferentes períodos após lesão por estimulação elétrica neuromuscular

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